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

Jennifer S. Fang, Cuiping Dai, David T. Kurjiaka, Janis M. Burt, Karen K. Hirschi

Research output: Contribution to journalArticle

20 Scopus citations

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. CONCLUSION-: 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.

Original languageEnglish (US)
Pages (from-to)362-368
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume33
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • TGF-β
  • connexin
  • endothelial cell
  • gap junction
  • mural cell development

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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