Targeting epigenetic regulators for treating diabetic nephropathy

Biochimie. 2022 Nov:202:146-158. doi: 10.1016/j.biochi.2022.08.001. Epub 2022 Aug 17.

Abstract

Diabetes is accompanied by the worsening of kidney functions. The reasons for kidney dysfunction mainly include high blood pressure (BP), high blood sugar levels, and genetic makeup. Vascular complications are the leading cause of the end-stage renal disorder (ESRD) and death of diabetic patients. Epigenetics has emerged as a new area to explain the inheritance of non-mendelian conditions like diabetic kidney diseases. Aberrant post-translational histone modifications (PTHMs), DNA methylation (DNAme), and miRNA constitute major epigenetic mechanisms that progress diabetic nephropathy (DN). Increased blood sugar levels alter PTHMs, DNAme, and miRNA in kidney cells results in aberrant gene expression that causes fibrosis, accumulation of extracellular matrix (ECM), increase in reactive oxygen species (ROS), and renal injuries. Histone acetylation (HAc) and histone deacetylation (HDAC) are the most studied epigenetic modifications with implications in the occurrence of kidney disorders. miRNAs induced by hyperglycemia in renal cells are also responsible for ECM accumulation and dysfunction of the glomerulus. In this review, we highlight the role of epigenetic modifications in DN progression and current strategies employed to ameliorate DN.

Keywords: Diabetes; Diabetic nephropathy; Epigenetics; Kidney failure.

Publication types

  • Review

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus*
  • Diabetic Nephropathies* / genetics
  • Epigenesis, Genetic
  • Histones
  • Humans
  • Hyperglycemia*
  • MicroRNAs* / genetics

Substances

  • Blood Glucose
  • Histones
  • MicroRNAs