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.

钙黏着蛋白是跨膜蛋白，通过促进粘附连接的形成来介导细胞间粘附。钙黏着蛋白的调节表达被认为在正常和患病的胎盘发育中都起着重要作用。Cadherin-11，也称为OB-cadherin，在人胎盘中表达，并已显示出与滋养层细胞分化的调控有关。我们已经证明，转化生长因子-β1（TGF-β1）促进人类滋养细胞的分化。另外，钙黏着蛋白11可以通过TGF-β1处理上调。然而，介导TGF-β1诱导的cadherin-11表达的潜在分子机制仍然未知。在这项研究中，我们证明了TGF-β1上调了人类滋养层细胞中钙黏着蛋白11的表达。TGF-β1处理可激活SMAD2 / 3信号通路。敲低SMAD2或SMAD3减弱了TGF-β1对钙黏着蛋白11表达的刺激作用。此外，转录因子Snail和Slug通过TGF-β1处理上调。有趣的是，仅敲低Snail才能消除TGF-β1诱导的cadherin-11表达上调。我们的结果表明，TGFβ1-SMAD2/ 3-Snail信号传导可能通过上调钙黏着蛋白11表达来促进人类滋养细胞的分化。