Gap junction communication mediates transforming growth factor-β activation and endothelial-induced mural cell differentiation

Karen K. Hirschi, Janis M. Burt, Kendal D. Hirschi, Cuiping Dai

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

During blood vessel assembly, endothelial cells recruit mesenchymal progenitors and induce their differentiation into mural cells via contact-dependent transforming growth factor-β (TGF-β) activation. We investigated whether gap junction channels are formed between endothelial cells and recruited mesenchymal progenitors and whether intercellular communication is necessary for endothelial-induced mural cell differentiation. Mesenchymal progenitors from Cx43-/- murine embryos and Cx43+/+ littermates were cocultured with prelabeled endothelial cells. Intracellular dye injection and dual whole-cell voltage clamp revealed that endothelial cells formed gap junction channels with Cx43+/+ but not Cx43-/- progenitors. In coculture with endothelial cells, Cx43-/- progenitors did not undergo mural cell differentiation as did Cx43 +/+ cells. Stable reexpression of Cx43 in Cx43-/- cells (reCx43) restored their ability to form gap junctions with endothelial cells and undergo endothelial-induced mural cell differentiation. Cocultures of endothelial cells and either Cx43+/+ or reCx43 mesenchymal cells produced activated TGF-β; endothelial-Cx43-/- cocultures did not. However, Cx43-/- cells did produce latent TGF-β and undergo mural cell differentiation in response to exogenous TGF-β1. These studies indicate that gap junction communication between endothelial and mesenchymal cells mediates TGF-β activation and subsequent mural cell differentiation.

Original languageEnglish (US)
Pages (from-to)429-437
Number of pages9
JournalCirculation research
Volume93
Issue number5
DOIs
StatePublished - Sep 5 2003

Keywords

  • Blood vessel formation
  • Endothelial cells
  • Gap junctions
  • Mural cell differentiation
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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