FGF-2-mediated FGFR1 signaling in human microvascular endothelial cells is activated by vaccarin to promote angiogenesis.
Biomed Pharmacother
; 95: 144-152, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28841454
ABSTRACT
Angiogenesis is a complex physiological process involving the growth of new capillaries. The impaired angiogenesis plays important roles in chronic wounds and ischaemic heart disease. Fibroblast growth factor 2 (FGF-2) exerts pro-angiogenic actions via activation of fibroblast growth factor receptor 1 (FGFR-1). We have identified that vaccarin increased the angiogenic activity of endothelial cells. In this study, we investigated whether FGF-2-mediated FGFR1 signaling pathway participated in vaccarin-mediated neovascularization formation. Human microvascular endothelial cells (HMEC)-1 were incubated with various doses of vaccarin. Our results showed that vaccarin dose-dependently up-regulated FGF-2 levels and phosphorylation of FGFR-1. Neutralization of FGF-2 with anti-FGF-2 antibody also abolished the proliferation, migration and tube formation of HMEC-1 cells induced by vaccarin. Both FGFR-1 inhibitor SU5402 and FGFR-1 siRNA blocked vaccarin-induced cell cycle progression and angiogenesis. The mouse Matrigel model study further unveiled that vaccarin stimulated the neovascularization and microvessel density in vivo, which was prevented by FGFR-1 inhibitor SU5402. Taken together, our results demonstrated for the first time that vaccarin was a novel inducer for FGF-2 expression, followed by phosphorylation of FGFR-1 and subsequent angiogenic behaviors in endothelial cells. Vaccarin may be a promising candidate of angiogenesis activator for neurovascular repair or therapy.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Flavonoides
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Regulação da Expressão Gênica
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Fator 2 de Crescimento de Fibroblastos
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Células Endoteliais
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Receptor Tipo 1 de Fator de Crescimento de Fibroblastos
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Glicosídeos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biomed Pharmacother
Ano de publicação:
2017
Tipo de documento:
Article