Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update

Ren Fail. 2017 Nov;39(1):474-483. doi: 10.1080/0886022X.2017.1313164.

Abstract

Epithelial-mesenchymal transition (EMT) is a tightly regulated process by which epithelial cells lose their hallmark epithelial characteristics and gain the features of mesenchymal cells. For podocytes, expression of nephrin, podocin, P-cadherin, and ZO-1 is downregulated, the slit diaphragm (SD) will be altered, and the actin cytoskeleton will be rearranged. Diabetes, especially hyperglycemia, has been demonstrated to incite podocyte EMT through several molecular mechanisms such as TGF-β/Smad classic pathway, Wnt/β-catenin signaling pathway, Integrins/integrin-linked kinase (ILK) signaling pathway, MAPKs signaling pathway, Jagged/Notch signaling pathway, and NF-κB signaling pathway. As one of the most fundamental prerequisites to develop ground-breaking therapeutic options to prevent the development and progression of diabetic kidney disease (DKD), a comprehensive understanding of the molecular mechanisms involved in the pathogenesis of podocyte EMT is compulsory. Therefore, the purpose of this paper is to update the research progress of these underlying signaling pathways and expound the podocyte EMT-related DKDs.

Keywords: Podocyte; diabetic kidney disease; epithelial–mesenchymal transition; hyperglycemia; molecular mechanism.

Publication types

  • Review

MeSH terms

  • Diabetic Nephropathies / physiopathology*
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Hyperglycemia / physiopathology*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Podocytes / metabolism
  • Podocytes / physiology*
  • Signal Transduction / physiology*
  • Tight Junction Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Tight Junction Proteins
  • nephrin