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FGF-2-mediated FGFR1 Signaling in Human Microvascular Endothelial Cells Is Activated by Vaccarin to Promote Angiogenesis

FGF-2-mediated FGFR1 Signaling in Human Microvascular Endothelial Cells Is Activated by Vaccarin to Promote Angiogenesis

Hai-Jian Sun, Wei-Wei Cai, Lei-Lei Gong, Xu Wang, Xue-Xue Zhu, Ming-Yu Wan, Pei-Yao Wang, Li-Ying Qiu

Biomed Pharmacother. 2017 Nov;95:144-152.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP53452167	Vaccarin		53452-16-7	Price
IAR4248664	FGF-2 human			Price

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