Bae Yun-Hee, Bae Moon-Kyoung, Kim Su-Ryun, Lee Jung Hoon, Wee Hee-Jun, Bae Soo-Kyung
Department of Physiology, School of Medicine, Pusan National University, Busan 602-739, South Korea.
Biochem Biophys Res Commun. 2009 Feb 6;379(2):206-11. doi: 10.1016/j.bbrc.2008.12.042. Epub 2008 Dec 25.
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.
脂肪因子在血管生成过程中作为血管生成调节因子已为人所知。最近，我们证实了一种新型脂肪因子内脂素具有血管生成活性。然而，关于内脂素诱导血管生成的潜在机制报道甚少。在本研究中，我们报告内脂素诱导的血管生成是由内皮成纤维细胞生长因子-2（FGF-2）介导的。内脂素增加了人内皮细胞中FGF-2 mRNA和蛋白的水平。细胞外信号调节激酶1/2（Erk1/2）通路抑制剂可阻止FGF-2表达的增强。此外，抑制FGF-2受体激酶或中和FGF-2功能可减少内脂素诱导的血管生成。综上所述，我们的结果表明内脂素诱导的内皮血管生成主要由两个连续步骤组成：内脂素诱导Erk1/2依赖性FGF-2基因表达以及随后FGF-2诱导的血管生成。这些数据进一步表明内脂素-FGF-2信号轴在调节内皮血管生成中起整体作用。
