Recent developments in epigenetics of acute and chronic kidney diseases

被引:87
|
作者
Reddy, Marpadga A. [1 ]
Natarajan, Rama [1 ]
机构
[1] City Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet Complicat, Duarte, CA 91010 USA
关键词
AKI; CKD; epigenetics; fibrosis; inflammation; metabolic memory; HYPOXIA-INDUCIBLE FACTOR; PREDICTIVE CHROMATIN SIGNATURES; ANGIOTENSIN-CONVERTING ENZYME; ALPHA-ENAC TRANSCRIPTION; SMOOTH-MUSCLE-CELLS; LONG-TERM OUTCOMES; GROWTH-FACTOR-BETA; DNA METHYLATION; HISTONE DEACETYLASE; DIABETIC-NEPHROPATHY;
D O I
10.1038/ki.2015.148
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:250 / 261
页数:12
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