4.7 Review

Unraveling the epigenetic landscape of glomerular cells in kidney disease

Journal

JOURNAL OF MOLECULAR MEDICINE-JMM
Volume 99, Issue 6, Pages 785-803

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00109-021-02066-2

Keywords

Epigenetics; Kidney disease; Podocytes; Mesangial cells; Glomerular endothelial cells

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/00573-4, 2019/10583-0]
  2. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior - Brasil (CAPES) [001]
  3. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, CNPq, Brazil [428482/2018-0]
  4. Competitive Research Grant from the Department of Biotechnology, Govt. of India [BT/PR33144/MED/30/2170/2019]
  5. Adhoc Research Project from Indian Council of Medical Research, Govt. of India [55/1/2019-BMS]

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Chronic kidney disease (CKD) is a major public health concern primarily caused by diabetes and/or hypertension, with high prevalence and mortality rates. Despite years of research, the pathogenesis of CKD remains unclear.
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.

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