학술논문
Lactadherin promotes VEGF-dependent neovascularization.
Document Type
Article
Author
Silvestre, Jean-Sébastien; Théry, Clotilde; Hamard, Ghislaine; Boddaert, Jacques; Aguilar, Barbara; Delcayre, Alain; Houbron, Christophe; Tamarat, Radia; Blanc-Brude, Olivier; Heeneman, Sylvia; Clergue, Michel; Duriez, Micheline; Merval, Régine; Lévy, Bernard; Tedgui, Alain; Amigorena, Sebastian; Mallat, Ziad
Source
Subject
*NEOVASCULARIZATION
*VASCULAR endothelial growth factors
*BLOOD-vessel development
*MILKFAT
*LABORATORY mice
*INTEGRINS
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Language
ISSN
1078-8956
Abstract
Vascular endothelial growth factor (VEGF)-induced blood vessel growth is involved in both physiological and pathological angiogenesis and requires integrin-mediated signaling. We now show that an integrin-binding protein initially described in milk-fat globule, MFG-E8 (also known as lactadherin), is expressed in and around blood vessels and has a crucial role in VEGF-dependent neovascularization in the adult mouse. Using neutralizing antibodies and lactadherin-deficient animals, we show that lactadherin interacts withavß3 andavß5 integrins and alters both VEGF-dependent Akt phosphorylation and neovascularization. In the absence of VEGF, lactadherin administration inducedavß3- andavß5-dependent Akt phosphorylation in endothelial cells in vitro and strongly improved postischemic neovascularization in vivo. These results show a crucial role for lactadherin in VEGF-dependent neovascularization and identify lactadherin as an important target for the modulation of neovascularization. [ABSTRACT FROM AUTHOR]