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Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):362-8. doi: 10.1161/ATVBAHA.112.255950. Epub 2012 Dec 6.

Connexin45 regulates endothelial-induced mesenchymal cell differentiation toward a mural cell phenotype.

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  • 1Yale Cardiovascular Research Center, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA.

Abstract

OBJECTIVE:

The focus of this study was to investigate the role of connexin (Cx) 45 in endothelial-induced mural cell differentiation.

METHODS AND RESULTS:

We created mural cell precursors that stably express only Cx45 in Cx43-deficient mesenchymal cells (ReCx45), and used our in vitro model of blood vessel assembly to assess the capacity of this Cx to support endothelial-induced mural cell differentiation. Lucifer Yellow dye injection and dual whole-cell patch clamping revealed that functional gap junctions exhibiting properties of Cx45-containing channels formed among ReCx45 transfectants, and between ReCx45 and endothelial cells. Heterocellular Cx45-containing gap junction channels enabled transforming growth factor-β activation and promoted the upregulation of mural cell-specific proteins in the mesenchymal precursors.

CONCLUSIONS:

These studies reveal a critical role for Cx45 in the regulation of endothelial-induced mural cell differentiation, which is consistent with the phenotype of Cx45-deficient embryos that exhibit dysregulated transforming growth factor-β and lack mural cell development.

PMID:
23220276
[PubMed - indexed for MEDLINE]
PMCID:
PMC3737426
Free PMC Article
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