Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and β-catenin

Kala Venkiteswaran, Kanyan Xiao, Susan Summers, Cathárine C. Calkins, Peter A. Vincent, Kevin Pumiglia, Andrew P. Kowalczyk

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

VE-cadherin is an endothelial-specific cadherin that plays a central role in vascular barrier function and angiogenesis. The cytoplasmic domain of VE-cadherin is linked to the cytoskeleton through interactions with the armadillo family proteins β-catenin and plakoglobin. Growing evidence indicates that β-catenin and plakoglobin play important roles in epithelial growth and morphogenesis. To test the role of these proteins in vascular cells, a replication-deficient retroviral system was used to express intercellular junction proteins and mutants in the human dermal microvascular endothelial cell line (HMEC-1). A mutant VE-cadherin lacking an adhesive extracellular domain disrupted endothelial barrier function and inhibited endothelial growth. In contrast, expression of exogenous plakoglobin or metabolically stable mutants of β-catenin stimulated HMEC-1 cell growth, which suggests that the β-catenin signaling pathway was active in HMEC-1 cells. This possibility was supported by the finding that a dominant-negative mutant of the transcription factor TCF-4, designed to inhibit β-catenin signaling, also inhibited HMEC-1 cell growth. These observations suggest that intercellular junction proteins function as components of an adhesion and signaling system that regulates vascular barrier function and growth.

Original languageEnglish (US)
Pages (from-to)C811-C821
JournalAmerican Journal of Physiology - Cell Physiology
Volume283
Issue number3 52-3
DOIs
StatePublished - Sep 2002

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cell Biology

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