TGF-β1 Up-Regulates Connexin43 Expression: A Potential Mechanism for Human Trophoblast Cell Differentiation

Connexin43 (Cx43)-mediated gap junctional intercellular communication (GJIC) are required for human trophoblast differentiation. To date, whether Cx43 mediates TGF-1-induced trophoblast differentiation has not been determined. We showed that treatment with TGF-1 increased Cx43 expression and GJIC in HTR-8/SVneo human trophoblast cells. In addition, Smad and ERK1/2 signaling pathways were involved in TGF-1-induced up-regulation of Cx43. Moreover, TGF-1 increased the expression of the syncytiotrophoblast marker, -hCG. Importantly, knockdown of Cx43 abolished the TGF-1-induced up-regulation of -hCG. Furthermore, overexpression of Cx43 up-regulated -hCG expression. These results provide evidence that Cx43 and GJIC activity are up-regulated by TGF-1 in human trophoblast cells, which subsequently contributes to TGF-1-induced trophoblast differentiation. J. Cell. Physiol. 230: 1558-1566, 2015. (c) 2015 Wiley Periodicals, Inc., A Wiley Company