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Glycemic Memories and the Epigenetic Component of Diabetic Nephropathy

  • Microvascular Complications-Nephropathy (B Roshan, Section Editor)
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Abstract

A strong case for the deregulation of epigenetic chromatin modifications in the development and progression of various chronic complications of diabetes has emerged from recent experimental observations. Clinical trials of type 1 and type 2 diabetes patients highlight the importance of early and intensive treatment and the prolonged damage of hyperglycemia on organs such as the kidney. The functional relationship between the regulation of chromatin architecture and persistent gene expression changes conferred by prior hyperglycemia represents an important avenue of investigation for explaining diabetic nephropathy. While several studies implicate epigenetic changes at the chromatin template in the deregulated gene expression associated with diabetic nephropathy, the molecular determinants of metabolic memory in renal cells remain poorly understood. There is now strong evidence from experimental animals and cell culture of persistent glucose-driven changes in vascular endothelial gene expression that may also have relevance for the microvasculature of the kidney. Exploration of epigenetic mechanisms underlying the hyperglycemic cue mediating persistent transcriptional changes in renal cells holds novel therapeutic potential for diabetic nephropathy.

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References

Recently published papers of particular interest are highlighted as: • Of importance •• Of major importance

  1. Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev. 2013;93:137–88.

    Article  PubMed  CAS  Google Scholar 

  2. Campos C. Chronic hyperglycemia and glucose toxicity: pathology and clinical sequelae. Postgrad Med. 2012;124:90–7.

    Article  PubMed  Google Scholar 

  3. Ayodele OE, Alebiosu CO, Salako BL. Diabetic nephropathy–a review of the natural history, burden, risk factors and treatment. J Natl Med Assoc. 2004;96:1445–54.

    PubMed  Google Scholar 

  4. Forbes JM, Fukami K, Cooper ME. Diabetic nephropathy: where hemodynamics meets metabolism. Exp Clin Endocrinol Diabetes. 2007;115:69–84.

    Article  PubMed  CAS  Google Scholar 

  5. Rhee I, Bachman KE, Park BH, et al. DNMT1 and DNMT3b cooperate to silence genes in human cancer cells. Nature. 2002;416:552–6.

    Article  PubMed  CAS  Google Scholar 

  6. Laird PW, Jaenisch R. The role of DNA methylation in cancer genetic and epigenetics. Annu Rev Genet. 1996;30:441–64.

    Article  PubMed  CAS  Google Scholar 

  7. Herman JG, Baylin SB. Promoter-region hypermethylation and gene silencing in human cancer. Curr Top Microbiol Immunol. 2000;249:35–54.

    Article  PubMed  CAS  Google Scholar 

  8. Balgkouranidou I, Liloglou T, Lianidou ES. Lung cancer epigenetics: emerging biomarkers. Biomark Med. 2013;7:49–58.

    Article  PubMed  CAS  Google Scholar 

  9. Waldmann T, Schneider R. Targeting histone modifications-epigenetics in cancer. Curr Opin Cell Biol. 2013.

  10. Webster AL, Yan MS, Marsden PA. Epigenetics and cardiovascular disease. Can J Cardiol. 2013;29:46–57.

    Article  PubMed  Google Scholar 

  11. Chin L, Gray JW. Translating insights from the cancer genome into clinical practice. Nature. 2008;452:553–63.

    Article  PubMed  CAS  Google Scholar 

  12. • Cooper ME, El-Osta A. Epigenetics: mechanisms and implications for diabetic complications. Circ Res. 2010;107:1403–13. Excellent review of the potential role of epigenetic mechansims and pathways implicated in diabetic vascular complications with insight into hyperglycemic memory.

    Article  PubMed  CAS  Google Scholar 

  13. [no authors listed] The Diabetes Control and Complications Trial (DCCT). Design and methodologic considerations for the feasibility phase. The DCCT Research Group. Diabetes 1986: 35: 530–545.

    Google Scholar 

  14. [no authors listed] The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993: 329: 977–986.

  15. [no authors listed] Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care 1999: 22: 99–111.

    Google Scholar 

  16. [no authors listed] Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000: 342: 381–389.

  17. [no authors listed] Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA 2003: 290: 2159–2167.

  18. Engerman RL, Kern TS. Progression of incipient diabetic retinopathy during good glycemic control. Diabetes. 1987;36:808–12.

    Article  PubMed  CAS  Google Scholar 

  19. Hammes HP, Klinzing I, Wiegand S, et al. Islet transplantation inhibits diabetic retinopathy in the sucrose-fed diabetic Cohen rat. Invest Ophthalmol Vis Sci. 1993;34:2092–6.

    PubMed  CAS  Google Scholar 

  20. El-Osta A, Brasacchio D, Yao D, et al. Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med. 2008;205:2409–17.

    Article  PubMed  CAS  Google Scholar 

  21. •• Brasacchio D, Okabe J, Tikellis C, et al. Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes. 2009;58:1229–36. This important study demonstrates that transcriptional activation of RELA is linked with persistent chromatin modifications that are regulated by histone modifying enzymes.

    Article  PubMed  CAS  Google Scholar 

  22. Ihnat MA, Thorpe JE, Kamat CD, et al. Reactive oxygen species mediate a cellular ‘memory’ of high glucose stress signalling. Diabetologia. 2007;50:1523–31.

    Article  PubMed  CAS  Google Scholar 

  23. Gilbertson DT, Liu J, Xue JL, et al. Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol. 2005;16:3736–41.

    Article  PubMed  Google Scholar 

  24. Steinke JM, Mauer M. Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. Pediatr Endocrinol Rev. 2008;5 Suppl 4:958–63.

    PubMed  Google Scholar 

  25. Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 2013;124:139–52.

    Article  CAS  Google Scholar 

  26. Henique C, Tharaux PL. Targeting signaling pathways in glomerular diseases. Curr Opin Nephrol Hypertens. 2012;21:417–27.

    Article  PubMed  CAS  Google Scholar 

  27. Mariappan MM. Signaling mechanisms in the regulation of renal matrix metabolism in diabetes. Exp Diabetes Res. 2012;201(2):749812.

    Google Scholar 

  28. Lan HY. Transforming growth factor-beta/Smad signalling in diabetic nephropathy. Clin Exp Pharmacol Physiol. 2012;39:731–8.

    Article  PubMed  CAS  Google Scholar 

  29. Gupta A, Gupta P, Biyani M. Targeted therapies in diabetic nephropathy: an update. J Nephrol. 2011;24:686–95.

    Article  PubMed  CAS  Google Scholar 

  30. Liu W, Lan T, Xie X, et al. S1P2 receptor mediates sphingosine-1-phosphate-induced fibronectin expression via MAPK signaling pathway in mesangial cells under high glucose condition. Exp Cell Res. 2012;318:936–43.

    Article  PubMed  CAS  Google Scholar 

  31. Ziyadeh FN. Mediators of diabetic renal disease: the case for tgf-Beta as the major mediator. J Am Soc Nephrol. 2004;15 Suppl 1:S55–7.

    Article  PubMed  CAS  Google Scholar 

  32. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54:1615–25.

    Article  PubMed  CAS  Google Scholar 

  33. Leehey DJ, Singh AK, Alavi N, et al. Role of angiotensin II in diabetic nephropathy. Kidney Int Suppl. 2000;77:S93–8.

    Article  PubMed  CAS  Google Scholar 

  34. Kang SW, Adler SG, Lapage J, et al. p38 MAPK and MAPK kinase 3/6 mRNA and activities are increased in early diabetic glomeruli. Kidney Int. 2001;60:543–52.

    Article  PubMed  CAS  Google Scholar 

  35. Brosius 3rd FC. New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev Endocr Metab Disord. 2008;9:245–54.

    Article  PubMed  CAS  Google Scholar 

  36. Kanwar YS, Wada J, Sun L, et al. Diabetic nephropathy: mechanisms of renal disease progression. Exp Biol Med (Maywood). 2008;233:4–11.

    Article  CAS  Google Scholar 

  37. Bondeva T, Ruster C, Franke S, et al. Advanced glycation end-products suppress neuropilin-1 expression in podocytes. Kidney Int. 2009;75:605–16.

    Article  PubMed  CAS  Google Scholar 

  38. Bondeva T, Roger T, Wolf G. Differential regulation of Toll-like receptor 4 gene expression in renal cells by angiotensin II: dependency on AP1 and PU.1 transcriptional sites. Am J Nephrol. 2007;27:308–14.

    Article  PubMed  CAS  Google Scholar 

  39. Yonemoto S, Machiguchi T, Nomura K, et al. Correlations of tissue macrophages and cytoskeletal protein expression with renal fibrosis in patients with diabetes mellitus. Clin Exp Nephrol. 2006;10:186–92.

    Article  PubMed  CAS  Google Scholar 

  40. • Zhang Q, Xiao X, Li M, et al. Gene expression profiling in glomeruli of diabetic nephropathy rat. Exp Biol Med (Maywood). 2012;237:903–11. This study examined transcriptome profiles of diabetic and control rat gloemruli. Furhermore, bioinformatic analysis revealed enrichment for pathways associated with diabetic nephropathy.

    Article  CAS  Google Scholar 

  41. Wada J, Zhang H, Tsuchiyama Y, et al. Gene expression profile in streptozotocin-induced diabetic mice kidneys undergoing glomerulosclerosis. Kidney Int. 2001;59:1363–73.

    Article  PubMed  CAS  Google Scholar 

  42. Brunskill EW, Potter SS. Gene expression programs of mouse endothelial cells in kidney development and disease. PLoS One. 2010;5:e12034.

    Article  PubMed  Google Scholar 

  43. • Brennan EP, Morine MJ, Walsh DW, et al. Next-generation sequencing identifies TGF-beta1-associated gene expression profiles in renal epithelial cells reiterated in human diabetic nephropathy. Biochim Biophys Acta. 2012;1822:589–99. This study describes transcriptome profiling of renal tubular epithelial cells following stimulation with TGF-β. Numerous transcriptional changes were confirmed in renal biopsies of patients with diabetic nephropathy.

    Article  PubMed  CAS  Google Scholar 

  44. Woroniecka KI, Park AS, Mohtat D, et al. Transcriptome analysis of human diabetic kidney disease. Diabetes. 2011;60:2354–69.

    Article  PubMed  CAS  Google Scholar 

  45. Tang W, Gao Y, Li Y, et al. Gene networks implicated in diabetic kidney disease. Eur Rev Med Pharmacol Sci. 2012;16:1967–73.

    PubMed  CAS  Google Scholar 

  46. [no authors listed] Effect of 6 months of strict metabolic control on eye and kidney function in insulin-dependent diabetics with background retinopathy. Steno study group. Lancet 1982: 1: 121–124.

  47. Feldt-Rasmussen B, Mathiesen ER, Deckert T. Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes. Lancet. 1986;2:1300–4.

    Article  PubMed  CAS  Google Scholar 

  48. [no authors listed] Blood glucose control and the evolution of diabetic retinopathy and albuminuria. A preliminary multicenter trial. The Kroc Collaborative Study Group. N Engl J Med 1984: 311: 365–372.

  49. Bending JJ, Viberti GC, Bilous RW, et al. Eight-month correction of hyperglycemia in insulin-dependent diabetes mellitus is associated with a significant and sustained reduction of urinary albumin excretion rates in patients with microalbuminuria. Diabetes. 1985;34 Suppl 3:69–73.

    PubMed  Google Scholar 

  50. Dahl-Jorgensen K, Brinchmann-Hansen O, Hanssen KF, et al. Effect of near normoglycaemia for two years on progression of early diabetic retinopathy, nephropathy, and neuropathy: the Oslo study. Br Med J (Clin Res Ed). 1986;293:1195–9.

    Article  CAS  Google Scholar 

  51. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993;329:304–9.

    Article  PubMed  CAS  Google Scholar 

  52. Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370:829–40.

    Article  PubMed  CAS  Google Scholar 

  53. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–72.

    Article  PubMed  CAS  Google Scholar 

  54. [no authors listed] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998: 352: 837–853.

  55. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577–89.

    Article  PubMed  CAS  Google Scholar 

  56. Gaede P, Tarnow L, Vedel P, et al. Remission to normoalbuminuria during multifactorial treatment preserves kidney function in patients with type 2 diabetes and microalbuminuria. Nephrol Dial Transplant. 2004;19:2784–8.

    Article  PubMed  Google Scholar 

  57. Gaede P, Vedel P, Parving HH, et al. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study. Lancet. 1999;353:617–22.

    Article  PubMed  CAS  Google Scholar 

  58. Murr R. Interplay between different epigenetic modifications and mechanisms. Adv Genet. 2010;70:101–41.

    Article  PubMed  CAS  Google Scholar 

  59. Svejstrup JQ. The RNA, polymerase II transcription cycle: cycling through chromatin. Biochim Biophys Acta. 2004;1677:64–73.

    Article  PubMed  CAS  Google Scholar 

  60. El-Osta A. Glycemic memory. Curr Opin Lipidol. 2012;23:24–9.

    Article  PubMed  CAS  Google Scholar 

  61. Reddy MA, Natarajan R. Role of epigenetic mechanisms in the vascular complications of diabetes. Subcell Biochem. 2012;61:435–54.

    Article  PubMed  Google Scholar 

  62. Fuks F, Hurd PJ, Wolf D, et al. The methyl-CpG-binding protein MeCP2 links DNA methylation to histone methylation. J Biol Chem. 2003;278:4035–40.

    Article  PubMed  CAS  Google Scholar 

  63. Meehan RR, Lewis JD, Bird AP. Characterization of MeCP2, a vertebrate DNA binding protein with affinity for methylated DNA. Nucleic Acids Res. 1992;20:5085–92.

    Article  PubMed  CAS  Google Scholar 

  64. Zhang Y, Ng HH, Erdjument-Bromage H, et al. Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. Genes Dev. 1999;13:1924–35.

    Article  PubMed  CAS  Google Scholar 

  65. Keating ST, El-Osta A. Epigenetic changes in diabetes. Clin Genet 2013. [epub ahead of print]

  66. Sapienza C, Lee J, Powell J, et al. DNA methylation profiling identifies epigenetic differences between diabetes patients with ESRD and diabetes patients without nephropathy. Epigenetics. 2011;6:20–8.

    Article  PubMed  CAS  Google Scholar 

  67. Bell CG, Teschendorff AE, Rakyan VK, et al. Genome-wide DNA methylation analysis for diabetic nephropathy in type 1 diabetes mellitus. BMC Med Genomics. 2010;3:33.

    Article  PubMed  Google Scholar 

  68. Roth SY, Denu JM, Allis CD. Histone acetyltransferases. Annu Rev Biochem. 2001;70:81–120.

    Article  PubMed  CAS  Google Scholar 

  69. Havas K, Whitehouse I, Owen-Hughes T. ATP-dependent chromatin remodeling activities. Cell Mol Life Sci. 2001;58:673–82.

    Article  PubMed  CAS  Google Scholar 

  70. Strahl BD, Allis CD. The language of covalent histone modifications. Nature. 2000;403:41–5.

    Article  PubMed  CAS  Google Scholar 

  71. Kassner I, Barandun M, Fey M et al. Crosstalk between SET7/9-dependent methylation and ARTD1-mediated ADP-ribosylation of histone H1.4. Epigenetics Chromatin 2013: 6: 1.

    Google Scholar 

  72. Tweedie-Cullen RY, Brunner AM, Grossmann J, et al. Identification of combinatorial patterns of post-translational modifications on individual histones in the mouse brain. PLoS One. 2012;7:e36980.

    Article  PubMed  CAS  Google Scholar 

  73. Muers M. Chromatin: a haul of new histone modifications. Nat Rev Genet. 2011;12:744.

    Article  PubMed  CAS  Google Scholar 

  74. Sayyed SG, Gaikwad AB, Lichtnekert J, et al. Progressive glomerulosclerosis in type 2 diabetes is associated with renal histone H3K9 and H3K23 acetylation, H3K4 dimethylation and phosphorylation at serine 10. Nephrol Dial Transplant. 2010;25:1811–7.

    Article  PubMed  CAS  Google Scholar 

  75. Gaikwad AB, Gupta J, Tikoo K. Epigenetic changes and alteration of Fbn1 and Col3A1 gene expression under hyperglycaemic and hyperinsulinaemic conditions. Biochem J. 2010;432:333–41.

    Article  PubMed  CAS  Google Scholar 

  76. • Sun G, Reddy MA, Yuan H, et al. Epigenetic histone methylation modulates fibrotic gene expression. J Am Soc Nephrol. 2010;21:2069–80. This important study implicates the Set7 lysine methyltransferase in mesangial gene expression in response to TGF-β and hyperglycemia. This is the first study to show that enzymes and histone modifications involved in vascular glycemic memory are responsive to glucose in renal cells.

    Article  PubMed  CAS  Google Scholar 

  77. Gotzsche O, Gundersen HJ, Osterby R. Irreversibility of glomerular basement membrane accumulation despite reversibility of renal hypertrophy with islet transplantation in early experimental diabetes. Diabetes. 1981;30:481–5.

    Article  PubMed  CAS  Google Scholar 

  78. Roy S, Sala R, Cagliero E, et al. Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci U S A. 1990;87:404–8.

    Article  PubMed  CAS  Google Scholar 

  79. Fang D, Guan H, Liu J, et al. Early intensive insulin therapy attenuates the p38 pathway in the renal cortex and indices of nephropathy in diabetic rats. Endocr J. 2012;59:81–90.

    Article  PubMed  CAS  Google Scholar 

  80. Okabe J, Orlowski C, Balcerczyk A, et al. Distinguishing hyperglycemic changes by Set7 in vascular endothelial cells. Circ Res. 2012;110:1067–76.

    Article  PubMed  CAS  Google Scholar 

  81. Starkey JM, Haidacher SJ, LeJeune WS, et al. Diabetes-induced activation of canonical and noncanonical nuclear factor-kappaB pathways in renal cortex. Diabetes. 2006;55:1252–9.

    Article  PubMed  CAS  Google Scholar 

  82. Keating ST, El-Osta A. Chromatin modifications associated with diabetes. J Cardiovasc Transl Res. 2012;5:399–412.

    Article  PubMed  Google Scholar 

  83. Syreeni A, El-Osta A, Forsblom C, et al. Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of diabetes complications in patients with type 1 diabetes. Diabetes. 2011;60:3073–80.

    Article  PubMed  CAS  Google Scholar 

  84. Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying mechanism for diabetic complications. Kidney Int Suppl. 2000;77:S26–30.

    Article  PubMed  CAS  Google Scholar 

  85. • Zhong Q, Kowluru RA. Epigenetic changes in mitochondrial superoxide dismutase in the retina and the development of diabetic retinopathy. Diabetes. 2011;60:1304–13. This study reveals a strong association between mitochondrial superoxide dismutase and the development of diabetic retinopathy.

    Article  PubMed  CAS  Google Scholar 

  86. Schmid H, Boucherot A, Yasuda Y, et al. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes. 2006;55:2993–3003.

    Article  PubMed  CAS  Google Scholar 

  87. Villeneuve LM, Reddy MA, Lanting LL, et al. Epigenetic histone H3 lysine 9 methylation in metabolic memory and inflammatory phenotype of vascular smooth muscle cells in diabetes. Proc Natl Acad Sci U S A. 2008;105:9047–52.

    Article  PubMed  CAS  Google Scholar 

  88. Hovind P, Tarnow L, Rossing K, et al. Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes. Diabetes Care. 2003;26:1258–64.

    Article  PubMed  Google Scholar 

  89. Yokoyama H, Okudaira M, Otani T, et al. Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan. Kidney Int. 2000;58:302–11.

    Article  PubMed  CAS  Google Scholar 

  90. El-Osta A. Remodeling is at the heart of chromatin: the heartaches of chromatin. Epigenetics. 2011;6:884–7.

    Article  PubMed  CAS  Google Scholar 

  91. Pirola L, Balcerczyk A, Tothill RW, et al. Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures of primary vascular cells. Genome Res. 2011;21:1601–15.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors acknowledge grant, scholarship, and fellowship support from the National Health and Medical Research Council (NHMRC), the Diabetes Australia Research Trust (DART), the Juvenile Diabetes Research Foundation International (JDRF), the National Heart Foundation of Australia (NHF), and the Australian Postgraduate Award (APA). A. E-O is a Senior Research Fellow supported by the NHMRC. This article was supported in part by the Victorian Government’s Operational Infrastructure Support Program.

Conflict of interest

Samuel T. Keating declares that he has no conflict of interest.

Assam El-Osta declares that he has no conflict of interest.

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Authors and Affiliations

  1. Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, 3004, Australia

    Samuel T. Keating & Assam El-Osta

  2. Epigenomics Profiling Facility, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, 3004, Australia

    Assam El-Osta

  3. Department of Pathology, The University of Melbourne, Melbourne, Victoria, 3010, Australia

    Assam El-Osta

  4. Faculty of Medicine, Monash University, Melbourne, Victoria, 3800, Australia

    Assam El-Osta

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  1. Samuel T. Keating
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Keating, S.T., El-Osta, A. Glycemic Memories and the Epigenetic Component of Diabetic Nephropathy. Curr Diab Rep 13, 574–581 (2013). https://doi.org/10.1007/s11892-013-0383-y

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