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J Cell Physiol. 2015 Jul;230(7):1558-66. doi: 10.1002/jcp.24902.

TGF-β1 up-regulates connexin43 expression: a potential mechanism for human trophoblast cell differentiation.

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Department of Obstetrics and Gynaecology, Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.


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.

[Indexed for MEDLINE]

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