4.7 Review

Recent developments in epigenetics of acute and chronic kidney diseases

Journal

KIDNEY INTERNATIONAL
Volume 88, Issue 2, Pages 250-261

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2015.148

Keywords

AKI; CKD; epigenetics; fibrosis; inflammation; metabolic memory

Funding

  1. National Institute of Health [R01 DK081705, R01 DK058191, R01 HL106089-01, R01 DK065073]
  2. Juvenile Diabetes Research Foundation [17-2012-480]
  3. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL106089] Funding Source: NIH RePORTER
  4. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK065073, R01DK081705, DP3DK106917, R01DK058191] Funding Source: NIH RePORTER

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The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies.

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