E-cadherin to N-cadherin switching in the TGF-β1 mediated retinal pigment epithelial to mesenchymal transition

Exp Eye Res. 2022 Jul:220:109085. doi: 10.1016/j.exer.2022.109085. Epub 2022 Apr 29.

Abstract

A serious form of ocular fibrotic disease is proliferative vitreoretinopathy (PVR) that can ultimately lead to blindness. While the pathogenesis of PVR is known to be closely tied to retinal pigment epithelial (RPE) cell epithelial-mesenchymal transition (EMT) characterized by E-cadherin downregulation and N-cadherin upregulation. Herein, we developed a model of transforming growth factor-β1 (TGF-β1)-induced EMT using human RPE (hRPE) cells as a tool for exploring the mechanistic basis for E-cadherin to N-cadherin switching. This analysis revealed that the loss of E-cadherin led to the separation of β-catenin from the catenin-cadherin complex whereupon it underwent nuclear entry to activate zinc finger E-box binding homeobox 1 (ZEB1), in turn promoting N-cadherin upregulation in this biological context. E-cadherin overexpression was sufficient to inhibit this EMT process and proliferation in RPE cells, further constraining their TGF-β1-induced apoptosis.

Keywords: E-cadherin; Epithelial-mesenchymal transition; N-cadherin; Proliferative vitreoretinopathy; Retinal pigment epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD
  • Cadherins* / metabolism
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigments / metabolism
  • Transforming Growth Factor beta1* / metabolism
  • Vitreoretinopathy, Proliferative* / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Retinal Pigments
  • TGFB1 protein, human
  • Transforming Growth Factor beta1