TGF-β1 up-regulates cadherin-11 expression through Snail: A potential mechanism for human trophoblast cell differentiation

Cell Signal. 2018 Mar:43:55-61. doi: 10.1016/j.cellsig.2017.12.004. Epub 2017 Dec 18.

Abstract

Cadherins are transmembrane proteins that mediate cell-cell adhesion by promoting the formation of adherens junctions. The regulated expression of cadherins is thought to play important roles in both normal and diseased placental development. Cadherin-11, also known as OB-cadherin, is expressed in human placenta and has been shown to be involved in regulation of trophoblast cell differentiation. We have demonstrated that transforming growth factor-beta1 (TGF-β1) promotes human trophoblast cell differentiation. In addition, cadherin-11 can be up-regulated by TGF-β1 treatment. However, the underlying molecular mechanisms that mediate TGF-β1-induced cadherin-11 expression remain unknown. In this study, we demonstrate that TGF-β1 up-regulates cadherin-11 expression in human trophoblast cells. TGF-β1 treatment activates SMAD2/3 signaling pathways. Knockdown of SMAD2 or SMAD3 attenuates the stimulatory effect of TGF-β1 on cadherin-11 expression. In addition, the transcription factors, Snail and Slug, are up-regulated by the TGF-β1 treatment. Interestingly, only knockdown of Snail abolishes the TGF-β1-induced up-regulation of cadherin-11 expression. Our results suggest that TGFβ1-SMAD2/3-Snail signaling could contribute to the human trophoblast cell differentiation by up-regulating cadherin-11 expression.

Keywords: Cadherin-11; Snail; TGF-β1; Trophoblast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / genetics*
  • Cadherins / metabolism
  • Cell Differentiation / drug effects*
  • Cell Line
  • Humans
  • Smad2 Protein / metabolism
  • Smad3 Protein / metabolism
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Trophoblasts / cytology*
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism*
  • Up-Regulation / drug effects*

Substances

  • Cadherins
  • SMAD2 protein, human
  • SMAD3 protein, human
  • Smad2 Protein
  • Smad3 Protein
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta1
  • osteoblast cadherin

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