Vascular smooth muscle cell growth-promoting factor/F-spondin inhibits angiogenesis via the blockade of integrin αvβ3 on vascular endothelial cells

Yoshito Terai, Mayumi Abe, Kaoru Miyamoto, Masamichi Koike, Motoo Yamasaki, Masatsugu Ueda, Minoru Ueki, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Vascular smooth muscle cell growth-promoting factor (VSGP) was originally isolated from bovine ovarian follicular fluid as a stimulator of vascular smooth muscle cell proliferation. Homology searches indicate that bovine and human VSGPs are orthologs of rat F-spondin. Here, we examined whether recombinant human VSGP/F-spondin affected the biological activities of endothelial cells. VSGP/F-spondin did not affect the proliferation of human umbilical vein endothelial cells (HUVECs); however, it did inhibit VEGF- or bFGF-stimulated HUVEC migration. To clarify the mechanism of this inhibitory effect, we examined the adhesion of HUVECs to extracellular matrix proteins. VSGP/F-spondin specifically inhibited the spreading of HUVECs on vitronectin via the functional blockade of integrin αvβ3. As a result, VSGP/F-spondin inhibited the tyrosine phosphorylation of focal adhesion kinase (FAK) when HUVECs were plated on vitronectin. Moreover, VSGP/F-spondin inhibited the activation of Akt when HUVECs on vitronectin were stimulated with VEGF. VSGP/F-spondin inhibited tube formation by HUVECs in vitro and neovascularization in the rat cornea in vivo. These results indicate that VSGP/F-spondin inhibits angiogenesis at least in part by the blockade of endothelial integrin αvβ3.

Original languageEnglish
Pages (from-to)394-402
Number of pages9
JournalJournal of Cellular Physiology
Volume188
Issue number3
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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