GSDMD-mediated pyroptosis: a critical mechanism of diabetic nephropathy

Expert Rev Mol Med. 2021 Dec 27:23:e23. doi: 10.1017/erm.2021.27.

Abstract

Pyroptosis is a recently identified mechanism of programmed cell death related to Caspase-1 that triggers a series of inflammatory reactions by releasing several proinflammatory factors such as IL-1β and IL-18. The process is characterised by the rupture of cell membranes and the release of cell contents through the mediation of gasdermin (GSDM) proteins. GSDMD is an important member of the GSDM family and plays a critical role in the two pathways of pyroptosis. Diabetic nephropathy (DN) is a microvascular complication of diabetes and a major cause of end-stage renal disease. Recently, it was revealed that GSDMD-mediated pyroptosis plays an important role in the occurrence and development of DN. In this review, we focus on two types of kidney cells, tubular epithelial cells and renal podocytes, to illustrate the mechanism of pyroptosis in DN and provide new ideas for the prevention, early diagnosis and molecular therapy of DN.

Keywords: Diabetic nephropathy; GSDMD; podocytes; pyroptosis; tubular epithelial cells.

Publication types

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

MeSH terms

  • Caspase 1 / metabolism
  • Diabetes Mellitus*
  • Diabetic Nephropathies* / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kidney / metabolism
  • Phosphate-Binding Proteins
  • Podocytes* / metabolism
  • Pyroptosis

Substances

  • GSDMD protein, human
  • Intracellular Signaling Peptides and Proteins
  • Phosphate-Binding Proteins
  • Caspase 1