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

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.