Urotensin Ⅱ promotes monocyte chemoattractant protein-1 expression in aortic adventitial fibroblasts of rat  

作　　者：Zhang Yonggang Bao Shilin Kuang Zejian Ma Yanjun Hu Yanchao Mao Yanyan 

机构地区：[1]Department of Cardiology, Second Affiliated Hospital, ShantouUniversity Medical College, Shantou, Guangdong 515041, China [2]Cardiovascular Laboratory, Centre for Translational Medicine,Shantou University Medical College, Shantou, Guangdong 515041,China [3]Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong 515041, China

出　　处：《Chinese Medical Journal》2014年第10期1907-1912,共6页中华医学杂志（英文版）

基　　金：This project was supported by grants from National Natural Science Foundation of China （No. 30971273 and No. 81270223） and Natural Science Foundation of Guangdong Province of China （No. 9151051501000016 and No. S2011010000450）.

摘　　要：Background Urotensin Ⅱ （Ull）,a potent vasoconstrictive peptide,is able to stimulate phenotypic differentiation of adventitial fibroblasts.This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 （MCP1） expression in rat aortic adventitial fibroblasts,so as to explore possible mechanisms in the development of vascular inflammation.Methods Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII （1010-10-7 mol/L） and inhibitors of signal transduction pathways for 1 to 24 hours.MCP-1 mRNA and protein expression and secretion were determined by RT-PCR,Western blotting analysis and enzyme-linked immunosorbent assay （ELISA）,respectively.Results UII dose-and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells,with maximal effect at 10-8 mol/L at 3 hours for mRNA expression,24 hours for protein expression in the cells,and 12 hours for protein secretion from the cells.Furthermore,the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411,Rho kinase inhibitor Y27632,protein kinase C （PKC） inhibitor H7,mitogen-activated protein kinase inhibitor PD98059,calcineurin inhibitor cyclosporine A,and the Ca2＋channel blocker nicardipine.Conclusion UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase,PKC,mitogen-activated protein kinase,calcineurin and Ca2＋ channel signal transduction,thus contributing to adventitial inflammation.Background Urotensin Ⅱ （Ull）,a potent vasoconstrictive peptide,is able to stimulate phenotypic differentiation of adventitial fibroblasts.This study aimed to determine the effect of UII on monocyte chemoattractant protein-1 （MCP1） expression in rat aortic adventitial fibroblasts,so as to explore possible mechanisms in the development of vascular inflammation.Methods Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII （1010-10-7 mol/L） and inhibitors of signal transduction pathways for 1 to 24 hours.MCP-1 mRNA and protein expression and secretion were determined by RT-PCR,Western blotting analysis and enzyme-linked immunosorbent assay （ELISA）,respectively.Results UII dose-and time-dependently promoted MCP-1 mRNA and protein expression and secretion in cells,with maximal effect at 10-8 mol/L at 3 hours for mRNA expression,24 hours for protein expression in the cells,and 12 hours for protein secretion from the cells.Furthermore,the UII effects were significantly inhibited by treatment with its receptor antagonist SB710411,Rho kinase inhibitor Y27632,protein kinase C （PKC） inhibitor H7,mitogen-activated protein kinase inhibitor PD98059,calcineurin inhibitor cyclosporine A,and the Ca2＋channel blocker nicardipine.Conclusion UII may stimulate MCP-1 expression in rat aortic adventitial fibroblasts through its receptor and Rho kinase,PKC,mitogen-activated protein kinase,calcineurin and Ca2＋ channel signal transduction,thus contributing to adventitial inflammation.

关 键 词：urotensin Ⅱ monocyte chemoattractant protein-1 adventitial fibroblasts signal transduction 

分 类 号：Q517[生物学—生物化学] Q516