Visfatin through STAT3 activation enhances IL-6 expression that promotes endothelial angiogenesis.
Signal transducer and activator of transcription 3 (STAT3) acts as a mediator and biomarker in endothelial activation. We have recently shown that a novel adipokine visfatin promotes endothelial angiogenesis. The present study was to determine whether visfatin affects STAT3 activity and to explore the potential target gene(s). Here, we found that visfatin induced the activation of STAT3, as characterized by increased tyrosine phosphorylation, nuclear translocation, and DNA-binding activity in human endothelial cells. In addition, visfatin significantly upregulated mRNA and protein levels of endothelial interleukin-6 (IL-6), which was blocked by a specific inhibitor of STAT3 signaling and by the transfection of siRNA specific for STAT3. Furthermore, visfatin-induced angiogenesis was reduced by the inhibition of STAT3 signaling or neutralization of IL-6 function, as measured by tube formation, rat aortic ring assay, and mouse Matrigel plug assay. Taken together, our results provide the first example of STAT3-dependent endothelial IL-6 induction by visfatin and of the role of IL-6 in mediating visfatin-induced angiogenesis.
Kim
Jee-Young
JY
Department of Physiology, School of Medicine, Yangsan Campus of Pusan National University, Yangsan, 626-870, South Korea.
Bae
Yun-Hee
YH
Bae
Moon-Kyoung
MK
Kim
Su-Ryun
SR
Park
Hyun-Joo
HJ
Wee
Hee-Jun
HJ
Bae
Soo-Kyung
SK
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; C508600:IL6 protein, human; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human; C504970:nicotinamide phosphoribosyltransferase, rat