DNA methylation and the potential role of demethylating agents in prevention of progressive chronic kidney disease

Publication Type:
Journal Article
FASEB Journal, 2018, 32 (10), pp. 5215 - 5226
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© 2018 American Society for Biochemistry and Molecular Biology Inc. All rights reserved. Chronic kidney disease (CKD) is a global epidemic, and itsmajor risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but alsomay independently lead to CKD by a variety ofmechanisms, including endocrine andmetabolic 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 theDNAsequence.Of these,DNAmethylation is the most studied. Epigenetic imprints, particularlyDNA methylation, are laid down during critical periods of fetal development, and they may provide a mechanism by whichmaternal-fetal transmissionof chronic diseaseoccurs.Ourcurrent review explores the evidence for the role of DNAmethylationinthedevelopment ofCKD,diabetickidneydisease,diabetes, andobesity.DNAmethylationhas been implicated in renal fibrosis-the final pathophysiologic pathway in the development of end-stage kidney disease-which supports the notion that demethylating agentsmay play a potential therapeutic role in preventing development and progression of CKD.
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