Professor Saad’ s research interest is in the area of metabolic and kidney disease. Her research aims to identify the mechanisms of how diabetic and non-diabetic kidney diseases develop and progresses. Her vision is to change the way how chronic kidney disease (CKD) is diagnosed and treated in order to reduce the health and economic burden of CKD in Australia and worldwide. As such she has developed multiple collaborations with national and international academics and several biotech companies to study the origin of CKD and potential interventions to prevent/reduce CKD development.
Professor Saad has been investigating the maternal influence on fetal programming of metabolic disease and CKD development in the offspring. Her research outcome has been featured on the MD Magazine-HCP live which reports the breaking news in medical research and on multiple press reports such as Medical Press, Get STEM, Medical News Today and U R The Voice UK. She has published extensively in the area of renal and metabolic disease and has obtained multiple national competitive grants and commercial support for her work and her students. Professor Saad is affiliated with Sydney University and the University of Technology Sydney. She teaches students in both universities. She has supervised multiple PhDs, Masters and honours students to completion, all of whom have had successful career post-graduation. She has strong multi-disciplinary collaborations and is engaged in animal and clinical research in collaboration with Professors Carol Pollock and Gregory Fulcher.
I have taken on administrative and leadership roles in the local and national research community. I am a member of the Australian and New Zealand Society of Nephrology, a member of the Science Advisory Board (Orlando) and Scientific Staff Council
I have acted as a guest editor for PPAR Research Journal, a PC2 manager, a medical student Interviewer, a TGA interviewer and a panel member for higher degree research students.
In addition, I have been involved in the management of the New Horizons Conference which involves the Kolling Institute, the University of Technology Sydney, Royal North Shore Hospital, The Woolcock Institute and The Centenary Institute for 14 years. I have served as a Chair of the New Horizons committee for 9 years and have received an Eminent contribution Award for my contribution.
I was also involved in the decisions making related to Research Support Services and Research Infrastructure across NSLHD/Kolling Institute/ Northern Clinical School, and have been responsible for the management of the Renal meetings and Kolling seminars.
I am a regular reviewer of international and national grants, manuscripts and PhD thesis’s in my research field.
Can supervise: YES
Current research interests: Maternal programing of disease, Epigenetics, Oxidative stress, Kidney fibrosis, diabetic nephropathy, medical device, Biomarkers, metabolic disease, obesity, smoking, type 1 and type 2 diabetes.
Past areas of research interest: Hematology, Breast cancer invasion, bone marrow environment.
I have been using research-oriented teaching method to encourage imaginative student inquiry using the latest research discoveries from my own research and the other leading research groups. I also mentor and coach junior staff in my group and within the department and encourage them to act in supervision roles to foster their career development. As such, my outstanding research teaching performance has been highly recommended by the Heads of School of Medicine and Science and the University of Sydney and university of Technology Sydney. To date, I have supervised 8 PhDs, 7 Masters and 1 honours student to completion affiliated to Sydney University or to the UTS where I hold an Honorary position as an Adjunct professor. All my students are highly regarded for their readiness of employment with their exceptional technical, communication and analytical skills. Many have received Early Carrer Fellowships and are research academics. I am currently supervising 4 PhD and one Master student affiliated with the University of Sydney and co-supervising another PhD and 2 Honours students affiliated with the UTS. In addition, I am involved in teaching undergraduate medical students (new MD program) at the University of Sydney. My teaching was recognised by multiple teaching awards from the Head of Schools of Medicine and Science and I received a Teaching Award from Sydney Medical School in 2016 for my contribution to teaching Medical Students. I also teach renal physiology and pathology at the University of Technology Sydney.
Li, G, Chan, YL, Sukjamnong, S, Anwer, AG, Vindin, H, Padula, M, Zakarya, R, George, J, Oliver, BG, Saad, S & Chen, H 2019, 'A Mitochondrial Specific Antioxidant Reverses Metabolic Dysfunction and Fatty Liver Induced by Maternal Cigarette Smoke in Mice', NUTRIENTS, vol. 11, no. 7.View/Download from: UTS OPUS or Publisher's site
Chan, YL, Wang, B, Chen, H, Ho, KF, Cao, J, Hai, G, Jalaludin, B, Herbert, C, Thomas, PS, Saad, S & Oliver, BGG 2019, 'Pulmonary inflammation induced by low-dose particulate matter exposure in mice.', American journal of physiology. Lung cellular and molecular physiology, vol. 317, no. 3, pp. L424-L430.View/Download from: UTS OPUS or Publisher's site
Air pollution is a ubiquitous problem and comprises gaseous and particulate matter (PM). Epidemiological studies have clearly shown that exposure to PM is associated with impaired lung function and the development of lung diseases, such as chronic obstructive pulmonary disease and asthma. To understand the mechanisms involved, animal models are often used. However, the majority of such models represent high levels of exposure and are not representative of the exposure levels in less polluted countries, such as Australia. Therefore, in this study, we aimed to determine whether low dose PM10 exposure has any detrimental effect on the lungs. Mice were intranasally exposed to saline or traffic-related PM10 (1μg or 5μg/day) for 3 wk. Bronchoalveolar lavage (BAL) and lung tissue were analyzed. PM10 at 1 μg did not significantly affect inflammatory and mitochondrial markers. At 5 μg, PM10 exposure increased lymphocytes and macrophages in BAL fluid. Increased NACHT, LRR and PYD domains-containing protein 3 (NLRP3) and IL-1β production occurred following PM10 exposure. PM10 (5 μg) exposure reduced mitochondrial antioxidant manganese superoxide (antioxidant defense system) and mitochondrial fusion marker (OPA-1), while it increased fission marker (Drp-1). Autophagy marker light-chain 3 microtubule-associated protein (LC3)-II and phosphorylated-AMPK were reduced, and apoptosis marker (caspase 3) was increased. No significant change of remodeling markers was observed. In conclusion, a subchronic low-level exposure to PM can have an adverse effect on lung health, which should be taken into consideration for the planning of roads and residential buildings.
Li, G, Chan, YL, Nguyen, LT, Mak, C, Zaky, A, Anwer, AG, Shi, Y, Nguyen, T, Pollock, CA, Oliver, BG, Saad, S & Chen, H 2019, 'Impact of maternal e-cigarette vapor exposure on renal health in the offspring', ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, vol. 1452, no. 1, pp. 65-77.View/Download from: UTS OPUS or Publisher's site
Nguyen, LT, Chen, H, Zaky, A, Pollock, C & Saad, S 2019, 'SIRT1 overexpression attenuates offspring metabolic and liver disorders as a result of maternal high-fat feeding.', The Journal of physiology, vol. 597, no. 2, pp. 467-480.View/Download from: UTS OPUS or Publisher's site
KEY POINTS:Maternal high-fat diet (MHF) consumption led to metabolic and liver disorders in male offspring, which are associated with reduced sirtuin (SIRT)1 expression and activity in the offspring liver SIRT1 overexpression in MHF offspring reduced their body weight and adiposity and normalized lipid metabolic markers in epididymal and retroperitoneal adipose tissues SIRT1 overexpression in MHF offspring improved glucose tolerance, as well as systemic and hepatic insulin sensitivity SIRT1 overexpression ameliorated MHF-induced lipogenesis, oxidative stress and fibrogenesis in the liver of offspring. ABSTRACT:Maternal obesity can increase the risk of metabolic disorders in the offspring. However, the underlying mechanism responsible for this is not clearly understood. Previous evidence implied that sirtuin (SIRT)1, a potent regulator of energy metabolism and stress responses, may play an important role. In the present study, we have shown, in C57BL/6 mice, that maternal high-fat diet (HFD) consumption can induce a pre-diabetic and non-alcoholic fatty liver disease phenotype in the offspring, associated with reduced SIRT1 expression in the hypothalamus, white adipose tissues (WAT) and liver. Importantly, the overexpression of SIRT1 in these offspring significantly attenuated the excessive accumulation of epididymal (Epi) white adipose tissue (WAT) and retroperitoneal (Rp)WAT (P < 0.001), glucose intolerance and insulin resistance (both P < 0.05) at weaning age. These changes were associated with the suppression of peroxisome proliferator-activated receptor gamma (PPAR)γ (P < 0.01), PPARγ-coactivator 1-alpha (P < 0.05) and sterol regulatory element-binding protein-1c in EpiWAT (P < 0.01), whereas there was increased expression of PPARγ in RpWAT (P < 0.05). In the liver, PPARγ mRNA expression, as well as Akt protein expression and activity, were increased (P < 0.05), whereas fatty acid synthase and carbohydrate response element binding protein were downregulated (P...
Nguyen, LT, Mak, CH, Chen, H, Zaky, AA, Wong, MG, Pollock, CA & Saad, S 2019, 'SIRT1 Attenuates Kidney Disorders in Male Offspring Due to Maternal High-Fat Diet.', Nutrients, vol. 11, no. 1.View/Download from: UTS OPUS or Publisher's site
Maternal obesity has been associated with kidney disorders in male offspring. Our previous studies have demonstrated that Sirtuin (SIRT)1, an essential regulator of metabolic stress responses, is suppressed in the offspring as the result of maternal high-fat diet (HFD) consumption, which is likely to underpin the adverse metabolic and renal outcomes. To examine if SIRT1 overexpression or activation early in life can protect the offspring kidney, wild-type (WT) and transgenic (Tg) offspring were born to the same diet-induced obese female C57BL/6 mice through breeding with hemizygous SIRT1-transgenic (Tg) male mice and examined for renal pathological changes. In separate experiments, SIRT1 activator SRT1720 (25 mg/kg/2 days i.p) was administrated in WT offspring over 6 weeks of postnatal high-fat diet exposure. The results show that offspring born to obese dams have increased kidney weight, higher levels of renal triglycerides, and increased expression of oxidative stress, inflammatory, and fibrotic markers, as well as increased albuminuria compared to offspring of control dams. Both SIRT1 overexpression and SRT1720 treatment attenuated renal lipid contents and expression of lipogenesis, oxidative stress, and inflammatory markers; however, fibrosis was modestly reduced and albuminuria was not affected. The findings suggest that SIRT1 therapy can ameliorate some pathological mechanisms of kidney programming due to maternal obesity but may not be sufficient to prevent the resulting chronic kidney injury.
Stangenberg, S, Nguyen, LT, Chan, YL, Zaky, A, Pollock, CA, Chen, H & Saad, S 2019, 'Maternal L-carnitine supplementation ameliorates renal underdevelopment and epigenetic changes in male mice offspring due to maternal smoking.', Clinical and experimental pharmacology & physiology, vol. 46, no. 2, pp. 183-193.View/Download from: UTS OPUS or Publisher's site
OBJECTIVES:Epidemiological and animal studies showed that L-carnitine (LC) supplementation can ameliorate oxidative stress-induced tissues damage. We have previously shown that maternal cigarette smoke exposure (SE) can increase renal oxidative stress in newborn offspring with postnatal kidney underdevelopment and renal dysfunction in adulthood, which were normalised by LC administration in the SE dams during pregnancy. Exposure to an adverse intrauterine environment may lead to alteration in the epigenome, a mechanism by which adverse prenatal conditions increase the susceptibility to chronic disease later in life. The current study aimed to determine whether maternal SE induces epigenetic changes in the offspring's kidney are associated with renal underdevelopment, and the protective effect of maternal LC supplementation. METHOD:Female Balb/c mice (7 weeks) were exposed to cigarette smoke (SE) or air (Sham) for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams received LC via drinking water (SE + LC, 1.5 mmol/L) throughout gestation and lactation. Male offspring were studied at postnatal day (P)1, P20, and 13 weeks. RESULTS:Maternal SE altered the expression of renal development markers glial cell line-derived neurotrophic factor and fibroblast growth factor 2, which were associated with increased renal global DNA methylation and DNA methyltransferase 1 mRNA expression at birth. These disorders were reversed by maternal LC administration. CONCLUSION:The effect of maternal SE on renal underdevelopment involves global epigenetic alterations from birth, which can be prevented by maternal LC supplementation.
Sukjamnong, S, Chan, YL, Zakarya, R, Nguyen, LT, Anwer, AG, Zaky, AA, Santiyanont, R, Oliver, BG, Goldys, E, Pollock, CA, Chen, H & Saad, S 2018, 'MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring.', Scientific reports, vol. 8, no. 1.View/Download from: UTS OPUS or Publisher's site
To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring's body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring's renal pathology, renal oxidative stress and mitochondrial density in mice offspring.
Chen, H, Chan, YL, Linnane, C, Mao, Y, Anwer, AG, Sapkota, A, Annissa, TF, Herok, G, Vissel, B, Oliver, BG, Saad, S & Gorrie, CA 2018, 'L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury.', Scientific reports, vol. 8, no. 1.View/Download from: UTS OPUS or Publisher's site
There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
Chen, H, Li, G, Chan, YL, Nguyen, T, van Reyk, D, Saad, S & Oliver, BG 2018, 'Modulation of neural regulators of energy homeostasis, and of inflammation, in the pups of mice exposed to e-cigarettes.', Neuroscience letters, vol. 684, pp. 61-66.View/Download from: UTS OPUS or Publisher's site
BACKGROUND:Maternal smoking can lead to perturbations in central metabolic regulators such as neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) signalling components in offspring. With the growing interest in e-cigarettes as a tobacco replacement, this short report assessed central metabolic regulation in offspring of mouse dams exposed to e-cigarettes. We examined the impact of continuous use of e-cigarettes, and e-cigarette replacement of tobacco cigarettes during pregnancy. Supplementation of an antioxidant l-carnitine was also co-used with tobacco cigarette in the mother to determine whether the impact of maternal tobacco smoking was oxidative stress driven. METHODS:Balb/c mice were exposed to either nicotine-containing (E-cig18) or nicotine-free (E-cig0) e-cigarette aerosols or tobacco smoke (SE) prior to mating and until their pups were weaned. After mating, two SE sub-groups were changed to E-cig18 exposure (Replacement), or supplementation l-carnitine while SE was continued. Male offspring were studied at weaning age. RESULTS:The offspring of E-cig0 dams were the heaviest with the most body fat. Replacing SE with E-cig18 during pregnancy resulted in offspring with significantly less body fat. E-cig0 offspring had significantly increased mRNA expression of brain NPY and iNOS. Maternal SE upregulated mRNA expression of NPY, NPY Y1 receptor, POMC downstream components, and iNOS expression, which were normalised in Replacement offspring, but only partially normalised with maternal L-carnitine supplementation during gestation and lactation. CONCLUSIONS:Maternal exposure to either tobacco and nicotine-free e-cigarettes lead to disturbances in the level of central homeostatic control markers in offspring, suggesting that maternal exposure to e-cigarettes is not without risks.
Glastras, SJ, Chen, H, Pollock, CA & Saad, S 2018, 'Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring.', Bioscience reports, vol. 38, no. 2.View/Download from: UTS OPUS or Publisher's site
Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.
Larkin, BP, Glastras, SJ, Chen, H, Pollock, CA & Saad, S 2018, 'DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 32, no. 10, pp. 5215-5226.View/Download from: UTS OPUS or Publisher's site
Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD. Epigenetic modifications are changes that regulate gene expression without altering the DNA sequence. Of these, DNA methylation is the most studied. Epigenetic imprints, particularly DNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by which maternal-fetal transmission of chronic disease occurs. Our current review explores the evidence for the role of DNA methylation in the development of CKD, diabetic kidney disease, diabetes, and obesity. DNA methylation has been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agents may play a potential therapeutic role in preventing development and progression of CKD.-Larkin, B. P., Glastras, S. J., Chen, H., Pollock, C. A., Saad, S. DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease.
Li, G, Saad, S, Oliver, BG & Chen, H 2018, 'Heat or Burn? Impacts of Intrauterine Tobacco Smoke and E-Cigarette Vapor Exposure on the Offspring's Health Outcome.', Toxics, vol. 6, no. 3.View/Download from: UTS OPUS or Publisher's site
Maternal smoking during pregnancy leads to gestational complications and organ disorders in the offspring. As nicotine replacement therapy is often ineffective for smoking cessation, pregnant women turn to alternatives such as heat-not-burn tobacco and e-cigarettes. Recently, the popularly of e-cigarettes has been increasing especially among the youth and pregnant women, mainly due to the advertisements claiming their safety. This has even led to some clinicians recommending their use during pregnancy. E-cigarettes heat e-liquid to produce an aerosol (e-vapor), delivering flavorings and nicotine to the user. However, e-vapor also contains toxins such as formaldehyde along with heavy metals and carcinogenic nitrosamines. In addition, specific flavoring compounds such as diacetyl can be toxic themselves or decompose into toxic compounds such as benzaldehydes. These compounds can induce toxicity, inflammation and oxidative stress in the mothers and can accumulate in the developing fetus, affecting intrauterine development. Recent animal studies suggest that maternal e-vapor exposure during pregnancy could cause respiratory and neurological disorders in the offspring. This review will examine the available literature to shed light on the current understanding of this problem-to-be from lessons learned in animal models.
Nguyen, LT, Chen, H, Mak, C, Zaky, A, Pollock, C & Saad, S 2018, 'SRT1720 attenuates obesity and insulin resistance but not liver damage in the offspring due to maternal and postnatal high-fat diet consumption.', American journal of physiology. Endocrinology and metabolism, vol. 315, no. 2, pp. E196-E203.View/Download from: UTS OPUS or Publisher's site
Recent studies indicate that sirtuin-1 (SIRT1), an important metabolic sensor and regulator of life span, plays a mechanistic role in maternal obesity-induced programming of metabolic disorders in the offspring. In this study we investigate whether SIRT1 activation in early childhood can mitigate metabolic disorders due to maternal and postnatal high-fat feeding in mice. Male offspring born to chow-fed (MC) or high fat diet-fed dams (MHF) were weaned onto postnatal chow or high-fat diet and treated with SRT1720 (25 mg/kg ip every 2 days) or vehicle control for 6 wk and examined for metabolic disorders. MHF exacerbated offspring body weight and insulin resistance in the offspring exposed to postnatal HFD (OHF). These metabolic changes were associated with reduced hepatic lipid droplet accumulation but increased plasma levels of alanine aminotransferase (ALT), a marker of liver damage. SRT1720 significantly decreased offspring body weight, adiposity, glucose intolerance, and hyperleptinemia due to OHF and reversed hyperinsulinemia and adipocyte hypertrophy due to the additive effects of MHF. Although SRT1720 suppresses liver lipogenesis, inflammation, and oxidative stress markers, it also reduces antioxidants and increased liver collagen deposition in OHF offspring independent of MHF. Hepatic steatosis was attenuated only in MC/OHF offspring in association with elevated plasma ALT levels. The study suggests that postnatal SRT1720 administration can mitigate obesity and insulin resistance in the offspring due to maternal and postnatal HFD exposure. However, the possibility of liver toxicity needs to be further examined.
Saad, S, Al-Odat, I, Chan, YL, McGrath, KC, Pollock, CA, Oliver, BG & Chen, H 2018, 'Maternal L-carnitine supplementation improves glucose and lipid profiles in female offspring of dams exposed to cigarette smoke.', Clinical and experimental pharmacology & physiology, vol. 45, no. 7, pp. 694-703.View/Download from: UTS OPUS or Publisher's site
Sex differences in disease susceptibility due to maternal programming have been reported. We previously observed that maternal smoking induced renal disease and neurological changes are restricted to males, while both male and female offspring develop metabolic disorders. We have also found that maternal L-carnitine supplementation during gestation and lactation can significantly improve glucose intolerance and hyperlipidaemia in male offspring. This study aimed to determine whether such beneficial effects can also occur in female offspring. Balb/c female mice were exposed to cigarette smoke (SE) 6 weeks prior to gestation, during gestation and lactation. A subgroup of the SE dams was given L-carnitine (1.5 mmol/L in drinking water) during gestation and lactation. Female offspring were studied at 20 days (weaning) and 13 weeks (adulthood). Maternal smoking increased liver weight (%) and blood glucose levels at 20 days, as well as glucose intolerance and plasma triglycerides levels at adulthood (P < .05). The hepatic lipid metabolic marker adipose triglyceride lipase was downregulated in the SE offspring at 20 days (P < .05). At 13 weeks, the hepatic pro-inflammatory markers IL-1β and TNF-α mRNA expression were upregulated, while the anti-inflammatory marker IL-10 mRNA expression was downregulated in the SE offspring (P < .05). Liver fibrosis was apparent at 20 days and 13 weeks. Maternal L-carnitine supplementation either normalised or suppressed the detrimental effects induced by maternal smoke exposure (P < .05). We conclude that maternal L-carnitine supplementation improves metabolic parameters in the female offspring of SE dams.
Stangenberg, S, Saad, S, Schilter, HC, Zaky, A, Gill, A, Pollock, CA & Wong, MG 2018, 'Lysyl oxidase-like 2 inhibition ameliorates glomerulosclerosis and albuminuria in diabetic nephropathy.', Scientific reports, vol. 8, no. 1.View/Download from: UTS OPUS or Publisher's site
Diabetic nephropathy is characterised by the excessive amount of extracellular matrix in glomeruli and tubulointerstitial space. Lysyl oxidase-like 2 (LOXL2) is elevated in renal fibrosis and known to play key roles in ECM stabilisation by facilitating collagen cross-links, epithelial to mesenchymal transition and myofibroblast activation. Thus, targeting LOXL2 may prove to be a useful strategy to prevent diabetic nephropathy. We explored the renoprotective effect of a selective small molecule LOXL2 inhibitor (PXS-S2B) in a streptozotocin-induced diabetes model. Diabetic mice were treated with PXS-S2B for 24 weeks and outcomes compared with untreated diabetic mice and with telmisartan treated animals as comparator of current standard of care. Diabetic mice had albuminuria, higher glomerulosclerosis scores, upregulation of fibrosis markers and increased renal cortical LOXL2 expression. Treatment with PXS-S2B reduced albuminuria and ameliorated glomerulosclerosis. This was associated with reduced expression of glomerular fibronectin and tubulointerstitial collagen I. The renoprotective effects of both PXS-S2B and telmisartan were more marked in the glomerular compartment than in the tubulointerstitial space. The study reveals that LOXL2 inhibition was beneficial in preserving glomerular structure and function. Thus, LOXL2 may be a potential therapeutic target in diabetic nephropathy.
Sukjamnong, S, Chan, YL, Zakarya, R, Saad, S, Sharma, P, Santiyanont, R, Chen, H & Oliver, BG 2017, 'Effect of long-term maternal smoking on the offspring's lung health.', American Journal of Physiology - Lung Cellular and Molecular Physiology, vol. 313, no. 2, pp. L416-L423.View/Download from: UTS OPUS or Publisher's site
Maternal smoking during pregnancy contributes to long-term health problems in offspring, especially respiratory disorders that can manifest in either childhood or adulthood. Receptors for advanced glycation end products (RAGE) are multiligand receptors abundantly localized in the lung, capable of responding to by-products of reactive oxygen species and proinflammatory responses. RAGE signaling is a key regulator of inflammation in cigarette smoking-related pulmonary diseases. However, the impact of maternal cigarette smoke exposure on lung RAGE signaling in the offspring is unclear. This study aims to investigate the effect of maternal cigarette smoke exposure (SE), as well as mitochondria-targeted antioxidant [mitoquinone mesylate (MitoQ)] treatment, during pregnancy on the RAGE-mediated signaling pathway in the lung of male offspring. Female Balb/c mice (8 wk) were divided into a sham group (exposed to air), an SE group (exposed to cigarette smoke), and an SE + MQ group (exposed to cigarette smoke with MitoQ supplement from mating). The lungs from male offspring were collected at 13 wk. RAGE and its downstream signaling, including nuclear factor-κB and mitogen-activated protein kinase family consisting of extracellular signal-regulated kinase 1, ERK2, c-JUN NH2-terminal kinase (JNK), and phosphorylated JNK, in the lung were significantly increased in the SE offspring. Mitochondrial antioxidant manganese superoxide dismutase was reduced, whereas IL-1β and oxidative stress response nuclear factor (erythroid-derived 2)-like 2 were significantly increased in the SE offspring. Maternal MitoQ treatment normalized RAGE, IL-1β, and Nrf-2 levels in the SE + MQ offspring. Maternal SE increased RAGE and its signaling elements associated with increased oxidative stress and inflammatory cytokines in offspring lungs, whereas maternal MitoQ treatment can partially normalize these changes.
Chan, YL, Saad, S, Al-Odat, I, Oliver, BG, Pollock, C, Jones, NM & Chen, H 2017, 'Maternal L-Carnitine Supplementation Improves Brain Health in Offspring from Cigarette Smoke Exposed Mothers.', Frontiers in Molecular Neuroscience, vol. 10, pp. 1-15.View/Download from: UTS OPUS or Publisher's site
Maternal cigarette smoke exposure (SE) causes detrimental changes associated with the development of chronic neurological diseases in the offspring as a result of oxidative mitochondrial damage. Maternal L-Carnitine administration has been shown to reduce renal oxidative stress in SE offspring, but its effect in the brain is unknown. Here, we investigated the effects of maternal L-Carnitine supplementation on brain markers of oxidative stress, autophagy, mitophagy and mitochondrial energy producing oxidative phosphorylation (OXPHOS) complexes in SE offspring. Female Balb/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation and lactation with or without L-Carnitine supplementation (1.5 mM in drinking water). In 1 day old male SE offspring, brain mitochondrial damage was suggested by increased mitochondrial fusion and reduced autophagosome markers; whereas at 13 weeks, enhanced brain cell damage was suggested by reduced fission and autophagosome markers, as well as increased apoptosis and DNA fragmentation markers, which were partially reversed by maternal L-Carnitine supplementation. In female SE offspring, enhanced mitochondrial regeneration was suggested by decreased fission and increased fusion markers at day 1. At 13 weeks, there was an increase in brain energy demand, oxidative stress and mitochondrial turnover, reflected by the protein changes of OXPHOS complex, fission and autophagosome markers, as well as the endogenous antioxidant, which were also partially normalized by maternal L-Carnitine supplementation. However, markers of apoptosis and DNA fragmentation were not significantly changed. Thus L-Carnitine supplementation may benefit the brain health of the offspring from smoking mothers.
Chan, YL, Saad, S, Machaalani, R, Oliver, BG, Vissel, B, Pollock, C, Jones, NM & Chen, H 2017, 'Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury.', Frontiers in Molecular Neuroscience, vol. 10, pp. 1-17.View/Download from: UTS OPUS or Publisher's site
Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE) can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3) and DNA fragmentation (TUNEL staining). Here, we aimed to investigate whether maternal SE leads to more severe neurological damage after HI brain injury in male offspring. Female BALB/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation, and lactation. At postnatal day 10, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen). At postnatal day 40-44, maternal SE reduced grip strength in grip traction and foot fault tests, which were also reduced by HI injury to similar levels regardless of the maternal group. Limb coordination was impaired by maternal SE which was not worsened by HI injury. Maternal SE increased anxiety level in the offspring, which was normalized by HI injury. Apoptosis markers were increased in different brain regions by maternal SE, with the cortex having further increased TUNEL by HI injury, along with increased markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI-induced cellular damage in male offspring well into adolescence.
Glastras, SJ, Chen, H, Tsang, M, Teh, R, McGrath, RT, Zaky, A, Chen, J, Wong, MG, Pollock, CA & Saad, S 2017, 'The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet.', PLoS ONE, vol. 12, no. 2, pp. 1-17.View/Download from: UTS OPUS or Publisher's site
AIMS/HYPOTHESIS: Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease. METHODS: Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32. RESULTS: HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity. CONCLUSION: Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.
Nguyen, LT, Chen, H, Pollock, C & Saad, S 2017, 'SIRT1 reduction is associated with sex-specific dysregulation of renal lipid metabolism and stress responses in offspring by maternal high-fat diet.', Scientific Reports, vol. 7, no. 1, pp. 1-13.View/Download from: UTS OPUS or Publisher's site
Rodent models of maternal obesity have been associated with kidney damage and dysfunction in offspring. However, the underlying mechanisms are yet to be elucidated. In this study, female rats were fed a high-fat diet (HFD) for 6 weeks prior to mating, throughout gestation and lactation; both male and female offspring were examined at weaning. Our results demonstrate that renal lipid deposition was increased in male offspring only, which is associated with reduced protein expression of Sirtuin (SIRT) 1, an essential regulator of lipid metabolism and stress response. Other components in its signalling network including phosphorylated 5'-AMP-activated protein kinase (pAMPKα), Forkhead box FOXO3a and Peroxisome proliferator-activated receptor (PPAR)γ coactivator 1-alpha (PGC-1α) were also downregulated. By contrast, in female offspring, renal fat/lipid distribution was unchanged in coupling with normal SIRT1 regulation. Specific autophagy and antioxidant markers were suppressed in both sexes. On the other hand, fibronectin and Collagen type IV protein expression was significantly higher in the offspring born HFD-fed dams, particularly in the males. Collectively, these findings suggest that maternal HFD consumption can induce sex-specific changes in offspring kidney lipid metabolism and stress responses at early ages, which may underpin the risk of kidney diseases later in life.
Nguyen, LT, Saad, S, Tan, Y, Pollock, C & Chen, H 2017, 'Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus.', Journal of Molecular Endocrinology, vol. 59, no. 1, pp. 81-92.View/Download from: UTS OPUS or Publisher's site
Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.
Chan, YL, Saad, S, Al-Odat, I, Zaky, AA, Oliver, B, Pollock, C, Li, W, Jones, NM & Chen, H 2016, 'Impact of maternal cigarette smoke exposure on brain and kidney health outcomes in female offspring.', Clinical and experimental pharmacology & physiology, vol. 43, pp. 1168-1176.View/Download from: UTS OPUS or Publisher's site
Increased oxidative stress in the brain can lead to increased sympathetic tone that may further induce kidney dysfunction. Previously we have shown that maternal cigarette smoke exposure (SE) leads to significantly increased oxidative stress and inflammation in both brain and kidney, as well as reduced brain and kidney mitochondrial activity. This is closely associated with significant kidney underdevelopment and abnormal function in adulthood in the male offspring. This study aimed to investigate the impact of maternal SE on brain and kidney health in the female offspring. In this study, the mouse dams were exposed to 2 cigarettes, twice daily for 6 weeks prior to gestation, during pregnancy and lactation. Brains and kidneys from the female offspring were collected at 20 days (P20) and 13 weeks (W13) and were subject to further analysis. We found that mRNA expression of brain inflammatory markers interleukin-1 receptor and Toll-like receptor 4 were significantly increased in the SE offspring at both P20 and W13. Their brain mitochondrial activity markers were however increased at W13 with increased antioxidant activity. Kidney development and function in the female SE offspring were not different from the control offspring. We concluded that although brain inflammatory markers were upregulated in the SE female offspring, they were protected from some of the indicators of brain oxidative stress, such as endogenous antioxidant and mitochondrial dysfunction, as well as abnormal kidney development and function in adulthood. This article is protected by copyright. All rights reserved.
Chan, YL, Saad, S, Pollock, C, Oliver, B, Al-Odat, I, Zaky, AA, Jones, N & Chen, H 2016, 'Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring', SCIENTIFIC REPORTS, vol. 6.View/Download from: UTS OPUS or Publisher's site
Chen, H, Chan, YL, Nguyen, LT, Mao, Y, de Rosa, A, Beh, IT, Chee, C, Oliver, B, Herok, G, Saad, S & Gorrie, C 2016, 'Moderate traumatic brain injury is linked to acute behaviour deficits and long term mitochondrial alterations', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol. 43, no. 11, pp. 1107-1114.View/Download from: UTS OPUS or Publisher's site
Glastras, SJ, Chen, H, McGrath, RT, Zaky, AA, Gill, AJ, Pollock, CA & Saad, S 2016, 'Effect of GLP-1 Receptor Activation on Offspring Kidney Health in a Rat Model of Maternal Obesity', SCIENTIFIC REPORTS, vol. 6.View/Download from: UTS OPUS or Publisher's site
Glastras, SJ, Chen, H, Teh, R, McGrath, RT, Chen, J, Pollock, CA, Wong, MG & Saad, S 2016, 'Mouse Models of Diabetes, Obesity and Related Kidney Disease.', PLoS ONE, vol. 11, no. 8, pp. 1-15.View/Download from: UTS OPUS or Publisher's site
Multiple rodent models have been used to study diabetic kidney disease (DKD). The purpose of the present study was to compare models of diabetes and obesity-induced metabolic syndrome and determine differences in renal outcomes. C57BL/6 male mice were fed either normal chow or high fat diet (HFD). At postnatal week 8, chow-fed mice were randomly assigned to low-dose streptozotocin (STZ, 55 mg/kg/day, five consecutive days) or vehicle control, whereas HFD-fed mice were given either one high-dose of STZ (100 mg/kg) or vehicle control. Intraperitoneal glucose tolerance tests were performed at Week 14, 20 and 30. Urinary albumin to creatinine ratio (ACR) and serum creatinine were measured, and renal structure was assessed using Periodic Acid Schiff (PAS) staining at Week 32. Results showed that chow-fed mice exposed to five doses of STZ resembled type 1 diabetes mellitus with a lean phenotype, hyperglycaemia, microalbuminuria and increased serum creatinine levels. Their kidneys demonstrated moderate tubular injury with evidence of tubular dilatation and glycogenated nuclear inclusion bodies. HFD-fed mice resembled metabolic syndrome as they were obese with dyslipidaemia, insulin resistance, and significantly impaired glucose tolerance. One dose STZ, in addition to HFD, did not worsen metabolic features (including fasting glucose, non esterified fatty acid, and triglyceride levels). There were significant increases in urinary ACR and serum creatinine levels, and renal structural changes were predominantly related to interstitial vacuolation and tubular dilatation in HFD-fed mice.
Glastras, SJ, Tsang, M, Teh, R, Chen, H, McGrath, RT, Zaky, AA, Pollock, CA & Saad, S 2016, 'Maternal Obesity Promotes Diabetic Nephropathy in Rodent Offspring', SCIENTIFIC REPORTS, vol. 6.View/Download from: UTS OPUS or Publisher's site
Gosnell, ME, Anwer, AG, Mahbub, SB, Menon Perinchery, S, Inglis, DW, Adhikary, PP, Jazayeri, JA, Cahill, MA, Saad, S, Pollock, CA, Sutton-Mcdowall, ML, Thompson, JG & Goldys, EM 2016, 'Quantitative non-invasive cell characterisation and discrimination based on multispectral autofluorescence features', Scientific Reports, vol. 6.View/Download from: Publisher's site
Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous autofluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from autofluorescence imaging has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent. Label-free classifications are validated by the analysis of Classification Determinant (CD) antigen expression. The versatility of our method is illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos.
Nguyen, LT, Chen, H, Pollock, CA & Saad, S 2016, 'Sirtuins-mediators of maternal obesity-induced complications in offspring?', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 30, no. 4, pp. 1383-1390.View/Download from: UTS OPUS or Publisher's site
Obesity is a complex metabolic disease, attributed to diverse and interactive genetic and environmental factors. The associated health consequences of obesity are pleiotropic, with individuals being more susceptible to chronic diseases such as type 2 diabetes mellitus, hypertension, and lipotoxicity-related chronic diseases. The contribution of maternal obesity to the offspring's predisposition to both obesity and its complications is increasingly recognized. Understanding the mechanisms underlying these "transmissible" effects is critical to develop therapeutic interventions to reduce the risk for "programmed" obesity. Sirtuins (SIRTs), particularly SIRT1 and SIRT3, are NAD(+)-dependent deacetylases that regulate metabolic balance and stress responses in both central and peripheral tissues, of which dysregulation is a well-established mediator for the development and effects of obesity. Nevertheless, their implication in the transmissible effects of maternal obesity across generations remains largely elusive. In this review, we examine multiple pathways and systems that are likely to mediate such effects, with particular emphasis on the role of SIRTs.-Nguyen, L. T., Chen, H., Pollock, C. A., Saad, S. Sirtuins-mediators of maternal obesity-induced complications in offspring?
Yaghobian, D, Don, AS, Yaghobian, S, Chen, X, Pollock, CA & Saad, S 2016, 'Increased sphingosine 1-phosphate mediates inflammation and fibrosis in tubular injury in diabetic nephropathy', Clinical and Experimental Pharmacology and Physiology, vol. 43, no. 1, pp. 56-66.View/Download from: Publisher's site
© 2016 John Wiley & Sons Australia, Ltd. Hyperglycemia induces all isoforms of transforming growth factor β (TGFβ), which in turn play key roles in inflammation and fibrosis that characterize diabetic nephropathy. Sphingosine 1-phosphate (S1P) is a signaling sphingolipid, derived from sphingosine by the action of sphingosine kinase (SK). S1P mediates many biological processes, which mimic TGFβ signaling. To determine the role of SK1 and S1P in inducing fibrosis and inflammation, and the interaction with TGFβ-1, 2 and 3 signalling in diabetic nephropathy, human proximal tubular cells (HK2 cells) were exposed to normal (5 mmol/L) or high (30 mmol/L) glucose or TGFβ-1, -2, -3 ± an SK inhibitor (SKI-II) or SK1 siRNA. Control and diabetic wild type (WT) and SK1-/- mice were studied. Fibrotic and inflammatory markers, and relevant downstream signalling pathways were assessed. SK1 mRNA and protein expression was increased in HK2 cells exposed to high glucose or TGFβ1,-2,-3. All TGFβ isoforms induced fibronectin, collagen IV and macrophage chemoattractant protein 1 (MCP1), which were reversed by both SKI-II and SK1 siRNA. Exposure to S1P increased phospho-p44/42 expression, AP-1 binding and NFkB phosphorylation. WT diabetic mice exhibited increased renal cortical S1P, fibronectin, collagen IV and MCP1 mRNA and protein expression compared to SK1-/- diabetic mice. In summary, this study demonstrates that inhibiting the formation of S1P reduces tubulointerstitial renal inflammation and fibrosis in diabetic nephropathy.
Chan, YL, Saad, S, Simar, D, Oliver, B, McGrath, K, Reyk, DV, Bertrand, PP, Gorrie, C, Pollock, C & Chen, H 2015, 'Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams', International Journal of Developmental Neuroscience, vol. 46, pp. 67-75.View/Download from: UTS OPUS or Publisher's site
Maternal obesity imposes significant health risks in the offspring including diabetes and dyslipidemia. We previously showed that the hypoglycaemic agent exendin-4 (Ex-4) administered from weaning can reverse the maternal impact of ‘transmitted disorders’ in such offspring. However daily injection for six-weeks was required and the beneficial effect may lapse upon drug withdrawal. This study aimed to investigate whether short term Ex-4 treatment during suckling period in a rodent model can reverse transmitted metabolic disorders due to maternal obesity.
Maternal obesity was induced in female Sprague Dawley rats by high-fat diet feeding for 6 weeks, throughout gestation and lactation. Female offspring were treated with Ex-4 (5 μg/kg/day) between postnatal day (P) 4 and 14. Female offspring were harvested at weaning (P20). Lipid and glucose metabolic markers were measured in the liver and fat. Appetite regulators were measured in the plasma and hypothalamus.
Maternal obesity significantly increased body weight, fat mass, and liver weight in the offspring. There was an associated inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression. It also increased the plasma gut hormone ghrelin and reduced glucagon-like peptide-1. Ex-4 treatment partially reversed the maternal impact on adiposity and impaired lipid metabolism in the offspring, with increased liver PGC1α and inhibition of FASN mRNA expression. Ex-4 treatment also increased the expression of a novel fat depletion gene a2-zinc-glycoprotein 1 in the fat tissue.
Short term Ex-4 treatment during the suckling period significantly improved the metabolic profile in the offspring from the obese mothers at weaning. Long-term studies are needed to follow such offspring to adulthood to examine the sustained effects of Ex-4 in p...
Glastras, SJ, Wong, MG, Chen, H, Zhang, J, Zaky, A, Pollock, CA & Saad, S 2015, 'FXR expression is associated with dysregulated glucose and lipid levels in the offspring kidney induced by maternal obesity', NUTRITION & METABOLISM, vol. 12.View/Download from: UTS OPUS or Publisher's site
Mreich, E, Chen, XM, Zaky, A, Pollock, CA & Saad, S 2015, 'The role of Krüppel-like factor 4 in transforming growth factor-β-induced inflammatory and fibrotic responses in human proximal tubule cells', Clinical and Experimental Pharmacology and Physiology, vol. 42, no. 6, pp. 680-686.View/Download from: Publisher's site
© 2015 Wiley Publishing Asia Pty Ltd. Krüppel-like factor 4 (KLF4) is known to mitigate inflammation in several cell types. Using human proximal tubule cells, the present study aimed to investigate the role of KLF4 in regulating transforming growth factor (TGF)-β1 induced inflammatory and fibrotic responses. Human kidney proximal tubular cells were exposed to high glucose, or TGF-β1 and KLF4 expressions were determined. Cells were then transfected with empty vector or KLF4 and exposed to 2-ng/mL TGF-β1 for up to 72 h. Inflammatory proteins (macrophage migration inhibitory factor and monocyte chemoattractant protein-1) and pro-fibrotic proteins (fibronectin and collagen IV) were measured after 72 h by enzyme-linked immunosorbent assay and western blot, respectively. To determine the relevance to in vivo models of chronic kidney disease, KLF4 protein expression in streptozotocin-induced diabetic mice was determined. Krüppel-like factor 4 messenger RNA (mRNA) levels were significantly reduced in high glucose-treated human kidney proximal tubular cells. High glucose increased TGF-β1 mRNA expression, which significantly increased migration inhibitory factor and monocyte chemoattractant protein-1 protein secretion. Transforming growth factor-β1 significantly increased fibronectin and collagen IV protein expression. The overexpression of KLF4 significantly reduced TGF-β-mediated increases in migration inhibitory factor and monocyte chemoattractant protein-1 but had no effect on TGF-β-mediated fibronectin and collagen IV mRNA and protein expression. The levels of KLF4 mRNA were significantly reduced in the diabetic kidney, and diabetic animals had a significant reduction in renal tubular expression of KLF4 proteins. This data suggest that KLF4 reduces inflammation induced by TGF-β1, suggesting a therapeutic role for KLF4 in diabetic nephropathy.
Nguyen, LT, Stangenberg, S, Chen, H, Al-Odat, I, Chan, YL, Gosnell, ME, Anwer, AG, Goldys, EM, Pollock, CA & Saad, S 2015, 'L-Carnitine reverses maternal cigarette smoke exposure-induced renal oxidative stress and mitochondrial dysfunction in mouse offspring.', American journal of physiology. Renal physiology, vol. 308, no. 7, pp. F689-F696.View/Download from: UTS OPUS or Publisher's site
Maternal smoking is associated with metabolic disorders, renal underdevelopment, and a predisposition to chronic kidney disease in offspring, yet the underlying mechanisms are unclear. By exposing female Balb/c mice to cigarette smoke for 6 wk premating and during gestation and lactation, we showed that maternal smoke exposure induced glucose intolerance, renal underdevelopment, inflammation, and albuminuria in male offspring. This was associated with increased renal oxidative stress and mitochondrial dysfunction at birth and in adulthood. Importantly, we demonstrated that dietary supplementation of l-carnitine, an amino acid shown to increase antioxidant defenses and mitochondrial function in numerous diseases, in smoke-exposed mothers during pregnancy and lactation significantly reversed the detrimental maternal impacts on kidney pathology in these male offspring. It increased SOD2 and glutathione peroxidase 1, reduced ROS accumulation, and normalized levels of mitochondrial preprotein translocases of the outer membrane, and oxidative phosphorylation complexes I-V in the kidneys of mouse progeny after intrauterine cigarette smoke exposure. These findings support the hypothesis that oxidative stress and mitochondrial dysfunction are closely linked to the adverse effects of maternal smoking on male offspring renal pathology. The results of our study suggest that l-carnitine administration in cigarette smoke-exposed mothers mitigates these deleterious renal consequences.
Stangenberg, S, Chen, H, Wong, MG, Pollock, CA & Saad, S 2015, 'Fetal programming of chronic kidney disease: the role of maternal smoking, mitochondrial dysfunction, and epigenetic modfification', AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, vol. 308, no. 11, pp. F1189-F1196.View/Download from: UTS OPUS or Publisher's site
Stangenberg, S, Nguyen, LT, Chen, H, Al-Odat, I, Killingsworth, MC, Gosnell, ME, Anwer, AG, Goldys, EM, Pollock, CA & Saad, S 2015, 'Oxidative stress, mitochondrial perturbations and fetal programming of renal disease induced by maternal smoking', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 64, pp. 81-90.View/Download from: UTS OPUS or Publisher's site
Zhang, J, Wong, MG, Wong, M, Gross, S, Chen, J, Pollock, C & Saad, S 2015, 'A Cationic-Independent Mannose 6-Phosphate Receptor Inhibitor (PXS64) Ameliorates Kidney Fibrosis by Inhibiting Activation of Transforming Growth Factor-beta(1)', PLOS ONE, vol. 10, no. 2.View/Download from: Publisher's site
Chen, H, Al-Odat, I, Chan, Y, Amgad, S, Wong, M, Gill, A, Pollock, C & Saad, S 2014, 'The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring', PLoS One, vol. 9, no. 7, pp. e103443-e103443.View/Download from: UTS OPUS or Publisher's site
This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders.
Chen, H, Simar, D, Pegg, K, Saad, S, Palmer, C & Morris, MJ 2014, 'Exendin-4 is effective against metabolic disorders induced by intrauterine and postnatal overnutrition in rodents', Diabetologia, vol. 57, no. 3.View/Download from: UTS OPUS or Publisher's site
Maternal obesity leads to increased adiposity, hyperlipidaemia and glucose intolerance in offspring. The analogue of glucagon-like peptide-1, exendin-4 (Ex-4), has been shown to induce weight loss in both adolescence and adulthood. We hypothesised that, in rats, daily injection of Ex-4 would reduce body fat and improve metabolic disorders in offspring from obese dams, especially those consuming a high-fat diet (HFD).
Female Sprague Dawley rats were fed chow or an HFD for 5 weeks before mating, and throughout gestation and lactation. At postnatal day 20, male pups from HFD-fed mothers were weaned onto chow or HFD and those from chow-fed mothers were fed chow. Within each dietary group, half of the pups were injected with Ex-4 (15 μg/kg/day i.p.) for 6 weeks, while the other half received saline.
Maternal obesity alone or combined with postweaning HFD consumption led to increased adiposity, hyperinsulinaemia, hyperlipidaemia, inflammation and impaired regulation of hypothalamic appetite regulators by glucose in offspring, while glucose intolerance was only observed in HFD-fed rats from obese dams. Ex-4 injection significantly reduced adiposity, hyperlipidaemia and insulin resistance in HFD-fed rats from obese dams. It also restored glucose tolerance and the lipid-lowering effect of blood glucose. However, Ex-4 did not change hypothalamic appetite regulation or the response of appetite regulators to hyperglycaemia. Liver and adipose inflammatory cytokine expression was significantly reduced by Ex-4.
Ex-4 reversed the detrimental impact of maternal obesity on lipid and glucose metabolism in offspring regardless of diet, supporting its potential application in reducing metabolic disorders in high-risk populations.
Wong, M, Saad, S, Zhang, J, Gross, S, Jarolimek, W, Schilter, H, Chen, JA, Gill, A, Pollock, CA & Wong, MG 2014, 'Semicarbazide-sensitive amine oxidase (SSAO) inhibition ameliorates kidney fibrosis in a unilateral uretal obstruction murine model', American Journal of Physiology - Renal Physiology, vol. 307, no. 8, pp. 908-916.View/Download from: Publisher's site
Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme known for its dual function in mediating inflammation and reactive oxygen species production. However, the role of SSAO inhibitors in limiting kidney fibrosis is unclear. We aimed to determine the effectiveness of a SSAO inhibitor (SSAOi; PXS4728A) as an antifibrotic agent using a 7-day unilateral ureteric obstruction (UUO) model of acute kidney fibrosis in 6- to 8-wk-old mice. The experimental groups were 1) Sham operated; 2) UUO; 3) UUO+SSAOi (2 mg/kg); 4) UUO+telmisartan, an angiotensin receptor blocker (3 mg/kg); and 5) UUO+SSAOi+telmisartan. Kidney tissue was analyzed for histological evidence of tubulointerstitial fibrosis, nitrotyrosine staining, and mRNA expression of markers associated with fibrosis and inflammation. Kidney SSAO activity was determined by radiometric [14C]benzylamine methodology. Our results show that SSAOi effectively suppresses UUO-mediated SSAO activity. Extracellular matrix markers, namely, fibronectin, collagen IV protein, and nitrotyrosine staining, were lower in UUO+SSAOi mice compared with untreated UUO mice. This was consistent with the attenuated mRNA expression of collagen IV and fibronectin. SSAOi effectively inhibited transforming growth factor-β1 (TGF-β1) and monocyte chemoattractant protein-1 (MCP-1) expression to a similar extent to that observed with telmisartan. Individually, SSAOi and telmisartan induced a reduction in interstitial leukocyte and macrophage accumulation. However, the combination of SSAOi and telmisartan was more effective at reducing inflammatory cell infiltration. These results demonstrate that SSAO inhibition significantly suppresses profibrotic and proinflammatory cytokine secretion, reduces oxidative stress, and limits inflammatory cell accumulation and extracellular matrix expression in an acute model of renal fibrosis.
Chen, H, Al-Odat, I, Pollock, C & Saad, S 2013, 'Fetal Programming of Renal Development-Influence of Maternal Smoking', Journal of Diabetes & Metabolism, vol. S9, pp. 1-7.View/Download from: UTS OPUS or Publisher's site
Smoking is a known risk factor for non-communicable illness including pulmonary disease, cardiovascular disease, and Type 2 diabetes. Smoking also contributes significantly to the rising `epidemic of chronic kidney disease. It is increasingly recognised that maternal programming of fetal development during pregnancy predisposes offspring to future disease. Maternal smoking, particularly in the first trimester, imposes a significant adverse impact on fetal renal development that determines the future risk of chronic kidney disease. Several mechanisms may contribute. Firstly, epigenetic modification of fetal nuclear or mitochondrial DNA, induced by intrauterine exposure to chemicals within the cigarette smoke, may result in an increased risk for metabolic and renal disorders. Secondly, nicotine and other chemicals within the cigarette smoke can cross the blood placental barrier concentrate in the fetus and result in direct toxicity. Thirdly, malnutrition due to the anorexigenic effect of smoking results in nutritional deficits in the fetus and impairs organ growth and development. 10-45% of pregnant women from diverse populations smoke during pregnancy. Hence it is considered a major and significant public health issue that imposes adverse health consequences not only to the pregnant women, but also inherited by their offspring, and potentially affecting future generations.
Pegg, K, Zhang, J, Pollock, C & Saad, S 2013, 'Combined Effects of PPAR gamma Agonists and Epidermal Growth Factor Receptor Inhibitors in Human Proximal Tubule Cells', PPAR RESEARCH.View/Download from: Publisher's site
Saad, S, Zhang, J, Yong, R, Yaghobian, D, Wong, MG, Kelly, DJ, Chen, XM & Pollock, CA 2013, 'Role of the EGF receptor in PPAR gamma-mediated sodium and water transport in human proximal tubule cells', DIABETOLOGIA, vol. 56, no. 5, pp. 1174-1182.View/Download from: Publisher's site
Wong, MYW, Saad, S, Pollock, C & Wong, MG 2013, 'Semicarbazide-sensitive amine oxidase and kidney disease', AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, vol. 305, no. 12, pp. F1637-F1644.View/Download from: Publisher's site
Yong, R, Chen, X-M, Shen, S, Vijayaraj, S, Ma, Q, Pollock, CA & Saad, S 2013, 'Plumbagin Ameliorates Diabetic Nephropathy via Interruption of Pathways that Include NOX4 Signalling', PLOS ONE, vol. 8, no. 8.View/Download from: Publisher's site
Chen, H, Saad, S, Sandow, SL & Bertrand, PP 2012, 'Cigarette smoking and brain regulation of energy homeostasis', Frontiers in Pharmacology, vol. 3, no. 147, pp. 1-8.View/Download from: UTS OPUS or Publisher's site
Cigarette smoking is an addictive behavior, and is the primary cause of cardiovascular and pulmonary disease, and cancer (among other diseases). Cigarette smoke contains thousands of components that may affect caloric intake and energy expenditure, although nicotine is the major addictive substance present, and has the best described actions. Nicotine exposure from cigarette smoke can change brain feeding regulation to reduce appetite via both energy homeostatic and reward mechanisms, causing a negative energy state which is characterized by reduced energy intake and increased energy expenditure that are linked to low body weight. These findings have led to the public perception that smoking is associated with weight loss. However, its effects at reducing abdominal fat mass (a predisposing factor for glucose intolerance and insulin resistance) are marginal, and its promotion of lean body mass loss in animal studies suggests a limited potential for treatment in obesity. Smoking during pregnancy puts pressure on the mothers metabolic system and is a significant contributor to adverse pregnancy outcomes.
Panchapakesan, U, Pollock, C & Saad, S 2011, 'Renal epidermal growth factor receptor: Its role in sodium and water homeostasis in diabetic nephropathy', CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, vol. 38, no. 2, pp. 84-88.View/Download from: Publisher's site
Saad, S, Stanners, SR, Yong, R, Tang, O & Pollock, CA 2010, 'Notch mediated epithelial to mesenchymal transformation is associated with increased expression of the Snail transcription factor', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 42, no. 7, pp. 1115-1122.View/Download from: Publisher's site
Sumual, S, Saad, S, Tang, O, Yong, R, McGinn, S, Chen, X-M & Pollock, CA 2010, 'Differential regulation of Snail by hypoxia and hyperglycemia in human proximal tubule cells', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 42, no. 10, pp. 1689-1697.View/Download from: Publisher's site
Panchapakesan, U, Pollock, C & Saad, S 2009, 'Review article: Importance of the kidney proximal tubular cells in thiazolidinedione-mediated sodium and water uptake', NEPHROLOGY, vol. 14, no. 3, pp. 298-301.View/Download from: Publisher's site
Saad, S, Agapiou, DJ, Chen, X-M, Stevens, V & Pollock, CA 2009, 'The role of Sgk-1 in the upregulation of transport proteins by PPAR-gamma agonists in human proximal tubule cells', NEPHROLOGY DIALYSIS TRANSPLANTATION, vol. 24, no. 4, pp. 1130-1141.View/Download from: Publisher's site
Stevens, VA, Saad, S, Poronnik, P, Fenton-Lee, CA, Polhill, TS & Pollock, CA 2008, 'The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells', NEPHROLOGY DIALYSIS TRANSPLANTATION, vol. 23, no. 6, pp. 1834-1843.View/Download from: Publisher's site
Stevens, VA, Saad, S, Chen, X-M & Pollock, CA 2007, 'The interdependence of EGF-R and SGK-1 in fibronectin expression in primary kidney cortical fibroblast cells', INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, vol. 39, no. 5, pp. 1047-1054.View/Download from: Publisher's site
Saad, S, Stevens, VA, Wassef, L, Poronnik, P, Kelly, DJ, Gilbert, RE & Pollock, CA 2005, 'High glucose transactivates the EGF receptor and up-regulates serum glucocorticoid kinase in the proximal tubule', KIDNEY INTERNATIONAL, vol. 68, no. 3, pp. 985-997.View/Download from: Publisher's site
Zafiriou, S, Stanners, SR, Saad, S, Polhill, TS, Poronnik, P & Pollock, CA 2005, 'Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts', JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, vol. 16, no. 3, pp. 638-645.View/Download from: Publisher's site
McGowan, EM, Saad, S, Bendall, LJ, Bradstock, KF & Clarke, CL 2004, 'Effect of progesterone receptor A predominance on breast cancer cell migration into bone marrow fibroblasts', BREAST CANCER RESEARCH AND TREATMENT, vol. 83, no. 3, pp. 211-220.View/Download from: Publisher's site
Polhill, TS, Saad, S, Poronnik, P, Fulcher, GR & Pollock, CA 2004, 'Short-term peaks in glucose promote renal fibrogenesis independently of total glucose exposure', AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, vol. 287, no. 2, pp. F268-F273.View/Download from: Publisher's site
McGinn, S, Saad, S, Poronnik, P & Pollock, CA 2003, 'High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase', AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, vol. 285, no. 4, pp. E708-E717.View/Download from: Publisher's site
McGinn, S, Saad, S, Poronnik, P & Pollock, CA 2003, 'High glucose-mediated effects on endothelial cell proliferation occur via p38 MAP kinase', American Journal of Physiology - Endocrinology and Metabolism, vol. 285, no. 4 48-4.
The mitogen-activated protein (MAP) kinases contribute to altered cell growth and function in a variety of disease states. However, their role in the endothelial complications of diabetes mellitus remains unclear. Human endothelial cells were exposed for 72 h to 5 mM (control) or 25 mM (high) glucose or 5 mM glucose plus 20 mM mannitol (osmotic control). The roles of p38 and p42/44 MAP kinases in the high glucose-induced growth effects were determined by assessment of phosphorylated MAP kinases and their downstream activators by Western blot and by pharmacological inhibition of these MAP kinases. Results were expressed as a percentage (means ± SE) of control. High glucose increased the activity of total and phosphorylated p38 MAP kinase (P < 0.001) and p42/44 MAP kinase (P < 0.001). Coexposure of p38 MAP kinase blocker with high glucose reversed the antiproliferative but not the hypertrophic effects associated with high-glucose conditions. Transforming growth factor (TGF)-β1 increased the levels of phosphorylated p38 MAP kinase, and p38 MAP kinase blockade reversed the antiproliferative effects of this cytokine. The high glucose-induced increase in phosphorylated p38 MAP kinase was reversed in the presence of TGF-β1 neutralizing antibody. Although hyperosmolarity also induced antiproliferation (P < 0.0001) and cell hypertrophy (P < 0.05), there was no change in p38 activity, and therefore inhibition of p38 MAP kinase had no influence on these growth responses. Blockade of p42/44 MAP kinase had no effect on the changes in endothelial cell growth induced by either high glucose or hyperosmolarity. High glucose increased p42/44 and p38 MAP kinase activity in human endothelial cells, but only p38 MAP kinase mediated the antiproliferative growth response through the effects of autocrine TGF-β1. High glucose-induced endothelial cell hypertrophy was independent of activation of the MAP kinases studied. In addition, these effects were independent of any increase in osmola...
Saad, S, Gottlieb, DJ, Bradstock, KF, Overall, CM & Bendall, LJ 2002, 'Cancer cell-associated fibronectin induces release of matrix metalloproteinase-2 from normal fibroblasts', CANCER RESEARCH, vol. 62, no. 1, pp. 283-289.
Saad, SR, Bendall, LJ, McGowan, EM, Gottlieb, DJ, Clarke, CL & Bradstock, KF 2000, 'Effects of progesterone on the migration of breast cancer cells within bone marrow stroma.', MOLECULAR BIOLOGY OF THE CELL, vol. 11, pp. 82A-82A.
Saad, S & Pollock, CA 2014, 'The role of snails in renal epithelial to mesenchymal transition' in Advances in Zoology Research, pp. 161-170.
© 2014 by Nova Science Publishers, Inc. All rights reserved. Epithelial-mesenchymal transition (EMT) is a highly controlled process involved in organogenesis, that is increasingly recognized as an integral part of tissue repair, organ fibrosis and cancer progression. In vitro data have shown that EMT is regulated by a complex signalling network. Recent in vivo data, in particular using tracing technologies, have conclusively demonstrated EMT in fibrotic kidney disease, and confirmed that EMT contributes to the pool of interstitial matrix-producing fibroblasts. In this review, we will summarize the known signalling pathways regulating EMT in renal proximal tubule cells following divergent insults, including exposure to high glucose, transforming growth factor β (TGF-β), angiotensin II and hypoxic conditions. We will also describe the signalling pathways/mediators differentially involved in the regulation of EMT in the fibrotic kidney, including Notch, Smad, integrin-linked kinase, Wnt/β-catenin and Erk1/2 and their convergent effects on Snail. The potential role of Snail as a common 'master switch' integrating various signal inputs in controlling EMT, its role in different models of renal pathology and potential therapeutic implications will be discussed.
Al-Odat, I, Chen, H, Sawiris, A, Pollock, C & Saad, S 2014, 'L-CARNITINE SUPPLEMENTATION DURING GESTATION AND LACTATION IMPROVE GLUCOSE INTOLERANCE INDUCED BY MATERNAL SMOKING IN THE OFFSPRING', NEPHROLOGY, WILEY-BLACKWELL, pp. 58-59.
Glastras, SJ, Chen, H, Pollock, C & Saad, S 2014, 'MATERNAL OBESITY IS ASSOCIATED WITH RENAL OXIDATIVE STRESS AND INFLAMMATION WHICH IS AMELIORATED BY THE GLP-1 RECEPTOR AGONIST EXENDIN-4', NEPHROLOGY, WILEY-BLACKWELL, pp. 62-62.
Gosnell, ME, Anwer, AG, Cassano, JC, Sue, CM, Mahbub, SB, Pernichery, SM, Inglis, DW, Nadort, A, Adhikary, PP, Jazayeri, JA, Cahill, MA, Saad, S, Pollock, C, Sutton-McDowall, ML, Thompson, JG & Goldys, EM 2014, 'Non-invasive detection and monitoring of biochemistry in cells and tissues by decomposing autofluorescence', Optics InfoBase Conference Papers.View/Download from: Publisher's site
© OSA 2016. Hyperspectral imaging based on endogenous contrast provides a new non-invasive method to characterise cells and tissues. Cellular content and maps of native fluorophores help monitor biological processes, with proper account of intrinsic cellular heterogeneity.
Nguyen, L, Stangerberg, S, Chan, Y, Al-Odat, I, Gosnell, M, Chen, H, Pollock, C & Saad, S 2014, 'L-CARNITINE REVERSED RENAL OXIDATIVE STRESS AND MITOCHONDRIAL DYSFUNCTION BY MATERNAL CIGARETTE SMOKE EXPOSURE IN MICE', NEPHROLOGY, WILEY-BLACKWELL, pp. 62-62.
Stangenberg, S, Nguyen, LT, Al-Odat, I, Chen, H, Killingsworth, M, Gosnell, ME, Anwer, A, Pollock, CA & Saad, S 2014, 'MATERNAL SMOKING INDUCES MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS IN OFFSPRING KIDNEYS', NEPHROLOGY, WILEY-BLACKWELL, pp. 57-57.
Wong, M, Zhang, J, Saad, S, Wong, MG & Pollock, C 2013, 'SEMICARBAZIDE-SENSITIVE AMINE OXIDASE INHIBITOR INHIBITS EXTRACELLULAR MATRIX DEPOSITION IN KIDNEY FIBROSIS', NEPHROLOGY, WILEY-BLACKWELL, pp. 51-51.
Saad, S, Chen, H, Al-Odat, I, Killingsworth, M & Pollock, CA 2012, 'RENAL DISORDERS INDUCED BY MATERNAL SMOKING', NEPHROLOGY, WILEY-BLACKWELL, pp. 54-54.
Saad, S, Chen, H, Pollock, CA & Wong, MG 2012, 'MATERNAL OBESITY RELATED RENAL INJURY IN MOTHER AND OFFSPRING IS MEDIATED THROUGH DOWN REGULATION OF RENAL FARNESOID X RECEPTOR (FXR) EXPRESSION', NEPHROLOGY, WILEY-BLACKWELL, pp. 59-60.
Yaghobian, D, Don, A, Yaghobian, S, Chen, X, Saad, S & Pollock, C 2012, 'The role of sphingosine 1-phosphate in the development of diabetic nephropathy', FEBS JOURNAL, 22nd IUBMB Congress/37th FEBS Congress, WILEY-BLACKWELL, Seville, SPAIN, pp. 147-148.
Yaghobian, D, Don, A, Yaghobian, S, Chen, X-M, Saad, S & Pollock, CA 2012, 'THE ROLE OF SPHINGOSINE 1-PHOSPHATE IN THE DEVELOPMENT OF DIABETIC NEPHROPATHY', NEPHROLOGY, WILEY-BLACKWELL, pp. 88-88.
Yong, R, Saad, S, Qi, Y, Vijayaraj, S, Huang, C, Chen, X & Pollock, CA 2012, 'THE INHIBITION OF NOX4 AMELIORATED THE FIBROTIC RESPONSES IN VITRO AND IN DIABETIC MOUSE KIDNEYS', NEPHROLOGY, WILEY-BLACKWELL, pp. 86-86.
Panchapakesan, U, Wong, M, Sumual, S, Yaghobian, D, Wu, H, Chadban, S, Pollock, C & Saad, S 2010, 'COMPENSATORY ADAPTIVE RESPONSES OF HUMAN PROXIMAL TUBULE CELL TO HIGH GLUCOSE', NEPHROLOGY, WILEY-BLACKWELL, pp. 65-65.
Wong, M, Saad, S, Qi, W, Chen, X & Pollock, C 2010, 'ACTIVATION OF FARNESOID X RECEPTORS (FXR) INHIBITS EXTRACELLULAR MATRIX (ECM) DEPOSITION IN HUMAN KIDNEY PROXIMAL TUBULAR EPITHELIAL CELLS (PTCS)', NEPHROLOGY, WILEY-BLACKWELL, pp. 66-67.
Mreich, E, Saad, S, Chen, XM & Pollock, CA 2009, 'MACROPHAGE MIGRATION INHIBITORY FACTOR STIMULATES ALTERNATIVELY ACTIVATED MACROPHAGES', NEPHROLOGY, WILEY-BLACKWELL PUBLISHING, INC, pp. A16-A16.
Saad, S, Yong, R, Kelly, DJ & Pollock, CA 2009, 'THE ROLE OF EGF RECEPTOR IN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA MEDIATED SODIUM AND WATER TRANSPORT IN HUMAN PROXIMAL TUBULE CELLS', NEPHROLOGY, WILEY-BLACKWELL PUBLISHING, INC, pp. A35-A35.
Sumual, S, Tang, O, Saad, S, Chen, X & Pollock, CA 2009, 'EFFECTS OF HYPOXIA AND HYPERGLYCEMIA ON REGULATION OF PROXIMAL TUBULAR CELL DEDIFFERENTIATION', NEPHROLOGY, WILEY-BLACKWELL PUBLISHING, INC, pp. A34-A35.
Saad, S, Agapiou, D, Chen, X-M, Stevens, V & Pollock, C 2008, 'THE ROLE OF SGK-1 IN PPAR gamma MEDIATED SODIUM AND WATER TRANSPORT IN HUMAN PROXIMAL TUBULE CELLS', NEPHROLOGY, WILEY-BLACKWELL, pp. A136-A136.
Sumual, S, Saad, S, Panchapakesan, U & Pollock, C 2008, 'THE EFFECT OF HYPOXIA AND HYPERGLYCEMIA ON NOTCH AND HIF1 alpha EXPRESSION IN HUMAN RENAL CORTICAL FIBROBLAST', NEPHROLOGY, WILEY-BLACKWELL, pp. A137-A138.
Saad, S, Stevens, V, Panchapakesan, U & Pollock, CA 2006, 'THE ROLE OF SGK-1 IN MEDIATING PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA INDUCED SODIUM TRANSPORT AND WATER TRANSPORT IN HUMAN PROXIMAL TUBULE CELLS', NEPHROLOGY, WILEY-BLACKWELL, pp. A45-A45.
Stanners, SR, Saad, S & Pollock, CA 2006, 'ENHANCED RENAL INTERSTITIAL FIBROSIS DUE TO INCREASED EPITHELIAL TO MESENCHYMAL TRANSFORMATION (EMT) IN PATIENTS WITH DIABETES MELLITUS', NEPHROLOGY, WILEY-BLACKWELL, pp. A4-A4.
Stanners, SR, Saad, S & Pollock, CA 2006, 'NOTCH SIGNALLING AMPLIFIES EPITHELIAL TO MESENCHYMAL TRANSFORMATION', NEPHROLOGY, WILEY-BLACKWELL, pp. A6-A6.
Qi, W, Saad, S, Twigg, S, Gilbert, RE, Poronnik, P & Pollock, CA 2003, 'The integrated actions of transforming growth factor-betal and connective tissue growth factor in renal fibrosis.', JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 36th Annual Meeting of the American-Society-of-Nephrology, LIPPINCOTT WILLIAMS & WILKINS, SAN DIEGO, CALIFORNIA, pp. 551A-551A.
Zafiriou, S, Saad, S, Poronnik, P & Pollock, CA 2002, 'Effects of a non-thiazolidinedione PPAR-gamma agonist on cell growth and matrix metalloproteinase (MMP) production in cells of the human renal cortex.', JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, LIPPINCOTT WILLIAMS & WILKINS, pp. 539A-540A.
I have made a substantial effort to promote my own research portfolio, within the science community both in Australia and internationally. Consequently, I have initiated, participated in, and sustained, a wide variety of collaborative research programs with Academia and Biotech, which I consider to represent a major contribution to my professional practice. These strategic liaisons have enabled me/my students to gain access to additional equipment, visit external laboratories to gain additional training, share ideas, develop new projects, increase my publication rate and get funding. These activities have helped me become a leading researcher in the field.
Prof Carol Pollock (Sydney University), Profs Kelly (University of Melbourne); Profs Harris (Westmead Millennium Institute); Prof Forbes (Matter Hospital); Dr Don (Prince of Wales clinical school); Assoc Prof Killingsworth (The Ingham Institute); Dr Hui (Mercy Hospital for Women); Assoc Prof Gill, Prof Morris and Prof Fulcher (Royal north Shore Hospital), Dr Chen and A/Prof Brian Oliver (UTS), Dr Gangadharan (Nepean Hospital), Prof Goldys (biophotonics, Macquarie University), Profs Packer and Paulsen (Biochemistry, MQ), Prof Nguyen and Dr Stirzaker (Garvan Institute), Dr Eliana Marino (St. Vincent Hospital).
Prof Levi (University of Colorado), Prof Murphy (University of Cambridge), Prof Hocher (University of Potsdam Germany), Prof Gu (Nanjing Drum Tower Hospital).
Commercial National and international collaborations:
Accugen Laboratories, Quantitative Biotechnology Pty Ltd, MitoQ PtY Ltd (New Zealand), MediKane Australia, Pharmaxis, BioRad, Sangui-Bio and Amgen.