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-β1-induced trophoblast differentiation has not been determined. We showed that treatment with TGF-β1 increased Cx43 expression and GJIC in HTR-8/SVneo human trophoblast cells. In addition, Smad and ERK1/2 signaling pathways were involved in TGF-β1-induced up-regulation of Cx43. Moreover, TGF-β1 increased the expression of the syncytiotrophoblast marker, β-hCG. Importantly, knockdown of Cx43 abolished the TGF-β1-induced up-regulation of β-hCG. Furthermore, overexpression of Cx43 up-regulated β-hCG expression. These results provide evidence that Cx43 and GJIC activity are up-regulated by TGF-β1 in human trophoblast cells, which subsequently contributes to TGF-β1-induced trophoblast differentiation.
(© 2015 Wiley Periodicals, Inc.)