Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factor.
Blood
; 111(5): 2674-80, 2008 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-18180379
ABSTRACT
Semaphorin 3A (Sema3A), a known inhibitor of axonal sprouting, also alters vascular patterning. Here we show that Sema3A selectively interferes with VEGF- but not bFGF-induced angiogenesis in vivo. Consistent with this, Sema3A disrupted VEGF- but not bFGF-mediated endothelial cell signaling to FAK and Src, key mediators of integrin and growth factor signaling; however, signaling to ERK by either growth factor was unperturbed. Since VEGF is also a vascular permeability (VP) factor, we examined the role of Sema3A on VEGF-mediated VP in mice. Surprisingly, Sema3A not only stimulated VEGF-mediated VP but also potently induced VP in the absence of VEGF. Sema3A-mediated VP was inhibited either in adult mice expressing a conditional deletion of endothelial neuropilin-1 (Nrp-1) or in wild-type mice systemically treated with a function-blocking Nrp-1 antibody. While both Sema3A- and VEGF-induced VP was Nrp-1 dependent, they use distinct downstream effectors since VEGF- but not Sema3A-induced VP required Src kinase signaling. These findings define a novel role for Sema3A both as a selective inhibitor of VEGF-mediated angiogenesis and a potent inducer of VP.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Permeabilidade Capilar
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Neovascularização Fisiológica
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Semaforina-3A
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Fator A de Crescimento do Endotélio Vascular
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article