The role of caveolin1 and sprouty1 in genistein's regulation of vascular smooth muscle cell and endothelial cell proliferation

• Published in: European journal of pharmacology Vol. 648; no. 1; pp. 153 - 161
• Main Authors: Xiang, QiuLing, Lin, GuiPing, Xu, JinWen, Zheng, ShuHui, Chen, SiJuan, Zhou, KeWen, Wang, TingHuai
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.12.2010; Elsevier
• Subjects: Angiotensin II - pharmacology; Animals; Biological and medical sciences; Cardiovascular system; Caveolin 1 - genetics; Caveolin 1 - metabolism; Caveolin1; Cell Proliferation - drug effects; Endothelial cell; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Female; Gene Expression Regulation, Enzymologic - drug effects; Genistein; Genistein - pharmacology; Medical sciences; Miscellaneous; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Pharmacology. Drug treatments; Phosphorylation - drug effects; Phytoestrogens - pharmacology; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Sprouty1; Vascular smooth muscle cell; Caveolin1; Vascular smooth muscle cell; Endothelial cell; Genistein; Sprouty1; Cell proliferation; Tyrosine kinase inhibitor; Smooth muscle; Isoflavone derivatives; Flavonoid; In vitro; Phytoestrogen; Polyphenol; Caveolin 1; Anti-astherosclerotic; Blood vessel; Phenols; Sprouty 1; Circulatory system; Mechanism of action
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.08.043

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.