Integrin β1 controls VE-cadherin localization and blood vessel stability

  • Hiroyuki Yamamoto
  • Manuel Ehling
  • Katsuhiro Kato
  • Kenichi Kanai
  • Max van Lessen
  • Maike Frye
  • Dagmar Zeuschner
  • Masanori Nakayama
  • Dietmar Vestweber
  • Ralf H Adams

Abstract

Angiogenic blood vessel growth requires several distinct but integrated cellular activities. Endothelial cell sprouting and proliferation lead to the expansion of the vasculature and give rise to a highly branched, immature plexus, which is subsequently reorganized into a mature and stable network. Although it is known that integrin-mediated cell-matrix interactions are indispensable for embryonic angiogenesis, little is known about the function of integrins in different steps of vascular morphogenesis. Here, by investigating the integrin β1-subunit with inducible and endothelial-specific gene targeting in the postnatal mouse retina, we show that β1 integrin promotes endothelial sprouting but is a negative regulator of proliferation. In maturing vessels, integrin β1 is indispensable for proper localization of VE-cadherin and thereby cell-cell junction integrity. The sum of our findings establishes that integrin β1 has critical functions in the growing and maturing vasculature, and is required for the formation of stable, non-leaky blood vessels.

Bibliographical data

Original languageEnglish
ISSN2041-1723
DOIs
Publication statusPublished - 10.03.2015
PubMed 25752958