Upregulation of fibroblast growth factor-2 by visfatin that promotes endothelial angiogenesis.
Adipokines have been known to act as angiogenic regulators in the process of angiogenesis. Recently, we have demonstrated that visfatin, a novel adipokine, has angiogenic activity. However, little has been reported on the underlying mechanism of visfatin-induced angiogenesis. In this study, we report that visfatin-induced angiogenesis is mediated by endothelial fibroblast growth factor-2 (FGF-2). Visfatin increased the levels of FGF-2 mRNA and protein in human endothelial cells. The enhancement in FGF-2 expression was prevented by an inhibitor of the extracellular signal-regulated kinase 1/2 (Erk1/2) pathway. Furthermore, visfatin-induced angiogenesis was reduced by inhibition of FGF-2 receptor kinase or by neutralization of FGF-2 function. Taken together, our results indicate that visfatin-induced endothelial angiogenesis is composed largely of two sequential steps: the induction of Erk1/2-dependent FGF-2 gene expression by visfatin and the subsequent FGF-2-induced angiogenesis. These data further suggest an integral role for visfatin-FGF-2 signaling axis in modulating endothelial angiogenesis.
Bae
Yun-Hee
YH
Department of Physiology, School of Medicine, Pusan National University, Busan 602-739, South Korea.
Bae
Moon-Kyoung
MK
Kim
Su-Ryun
SR
Lee
Jung Hoon
JH
Wee
Hee-Jun
HJ
Bae
Soo-Kyung
SK
D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018919:Neovascularization, Physiologic; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D016207:Cytokines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3