期刊
CELLULAR SIGNALLING
卷 43, 期 -, 页码 55-61出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2017.12.004
关键词
Cadherin-11; Snail; TGF-beta 1; Trophoblast cells
类别
资金
- Foundation Grant from the Canadian Institutes of Health Research [FDN-143317]
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-betal (TGF-beta 1) promotes human trophoblast cell differentiation. In addition, cadherin-11 can be up-regulated by TGF-beta 1 treatment. However, the underlying molecular mechanisms that mediate TGF-beta 1-induced cadherin-11 expression remain unknown. In this study, we demonstrate that TGF-beta 1 up-regulates cadherin-11 expression in human trophoblast cells. TGF-beta 1 treatment activates SMAD2/3 signaling pathways. Knockdown of SMAD2 or SMAD3 attenuates the stimulatory effect of TGF-beta 1 on cadherin-11 expression. In addition, the transcription factors, Snail and Slug, are up-regulated by the TGF-beta 1 treatment. Interestingly, only knockdown of Snail abolishes the TGF-beta 1-induced up-regulation of cadherin-11 expression. Our results suggest that TGF-beta 1-SMAD2/3-Snail signaling could contribute to the human trophoblast cell differentiation by up regulating cadherin-11 expression.
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