The role of caveolin1 and sprouty1 in genistein's regulation of vascular smooth muscle cell and endothelial cell proliferation.
Genistein prevents atherosclerosis by exerting protective effects on blood vessels. The aim of this study is to investigate the role of caveolin1 and sprouty1 in the regulation of proliferation of vascular smooth muscle cell (VSMC) and endothelial cell by genistein. Using thiazolyl blue tetrazolium bromide(MTT) and [3H]-TdR assay, we found genistein inhibited angiotensin II-induced proliferation in primary cultured VSMC while it stimulated proliferation of quiescent endothelial cells. The effects were attenuated by caveolin1 or sprouty1 siRNA. Western blot analysis indicated that genistein attenuated the phosphorylation of extracellular regulated kinase1/2(ERK1/2) in angiotensin II-induced proliferated VSMC but stimulated the phosphorylation of ERK1/2 in quiescent endothelial cell. Double staining immunofluorescence identified caveolin1 and sprouty1 coexpressed in the cytoplasm of both VSMC and endothelial cell. Genistein increased the expression of caveolin1, p-caveolin1 and sprouty1 in VSMC, while it had opposite effects in quiescent endothelial cell. Co-immunoprecipitation suggested that genistein exerted its effects through interaction of caveolin1 and sprouty1. Our results demonstrate that the inhibition of angiotensin II-induced proliferation of VSMC and stimulation of quiescent endothelial cell by genistein are regulated by caveolin1 and sprouty1, which are implemented through Ras/MAPK pathway.
Xiang
QiuLing
Q
Department of Physiology, Zhongshan Medical School, Sun Yat-Sen University, 74 ZhongShan Rd 2, GuangZhou 510080, People's Republic of China.
Lin
GuiPing
G
Xu
JinWen
J
Zheng
ShuHui
S
Chen
SiJuan
S
Zhou
KeWen
K
Wang
TingHuai
T
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D051242:Caveolin 1; D009419:Nerve Tissue Proteins; D048789:Phytoestrogens; C404992:Spry2 protein, rat; D000804:Angiotensin II; D019833:Genistein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3