Unraveling the epigenetic landscape of glomerular cells in kidney disease

J Mol Med (Berl). 2021 Jun;99(6):785-803. doi: 10.1007/s00109-021-02066-2. Epub 2021 Mar 24.

Abstract

Chronic kidney disease (CKD) is a major public health concern and its prevalence and incidence are rising quickly. It is a non-communicable disease primarily caused by diabetes and/or hypertension and is associated with high morbidity and mortality. Despite decades of research efforts, the pathogenesis of CKD remains a puzzle with missing pieces. Understanding the cellular and molecular mechanisms that govern the loss of kidney function is crucial. Abrupt regulation of gene expression in kidney cells is apparent in CKD and shown to be responsible for disease onset and progression. Gene expression regulation extends beyond DNA sequence and involves epigenetic mechanisms including changes in DNA methylation and post-translational modifications of histones, driven by the activity of specific enzymes. Recent advances demonstrate the essential participation of epigenetics in kidney (patho)physiology, as its actions regulate both the integrity of cells but also triggers deleterious signaling pathways. Here, we review the known epigenetic processes regulating the complex filtration unit of the kidney, the glomeruli. The review will elaborate on novel insights into how epigenetics contributes to cell injury in the CKD setting majorly focusing on kidney glomerular cells: the glomerular endothelial cells, the mesangial cells, and the specialized and terminally differentiated podocyte cells.

Keywords: Epigenetics; Glomerular endothelial cells; Kidney disease; Mesangial cells; Podocytes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers
  • DNA Methylation
  • Disease Susceptibility*
  • Endothelial Cells / metabolism
  • Epigenesis, Genetic*
  • Gene Expression Regulation*
  • Histones / metabolism
  • Humans
  • Kidney Diseases / etiology*
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Kidney Glomerulus / cytology*
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Mesangial Cells / metabolism
  • Podocytes / metabolism
  • Protein Processing, Post-Translational

Substances

  • Biomarkers
  • Histones