Homocysteine Induces Smooth Muscle Cell Proliferation Through Differential Regulation of Cyclins A and D1 Expression

被引:49
作者
Chiang, Jui-Kun [2 ,3 ]
Sung, Mao-Lin [4 ]
Yu, Hong-Ren [5 ]
Chang, Hsin-I [1 ]
Kuo, Hsing-Chun [6 ,7 ]
Tsai, Tzung-Chieh [8 ]
Yen, Chia-Kuang [4 ]
Chen, Cheng-Nan [1 ]
机构
[1] Natl Chiayi Univ, Dept Biochem Sci & Technol, Chiayi 600, Taiwan
[2] Buddhist Dalin Tzu Chi Gen Hosp, Dept Family Med, Chiayi, Taiwan
[3] Nanhua Univ, Dept Nat Biotechnol, Chiayi, Taiwan
[4] St Martin De Porres Hosp, Dept Cardiol, Chiayi, Taiwan
[5] Chang Gung Univ, Coll Med, Dept Pediat, Chang Gung Mem Hosp,Kaohsiung Med Ctr, Tao Yuan, Taiwan
[6] Chang Gung Inst Technol Chiayi Campus, Inst Nursing, Chiayi, Taiwan
[7] Chang Gung Inst Technol Chiayi Campus, Dept Nursing, Chiayi, Taiwan
[8] Natl Chiayi Univ, Dept Microbiol & Immunol, Chiayi 600, Taiwan
关键词
PROTEIN-KINASE PATHWAYS; GROWTH-FACTOR RECEPTOR; SIGNALING PATHWAYS; SHEAR-STRESS; FACTOR-BB; C-FOS; ACTIVATION; 3-KINASE; MECHANISMS; INDUCTION;
D O I
10.1002/jcp.22415
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
The mechanism of homocysteine-induced cell proliferation in human vascular smooth muscle cells (SMCs) remains unclear. We investigated the molecular mechanisms by which homocysteine affects the expression of cyclins A and D1 in human umbilical artery SMCs (HUASMCs). Homocysteine treatment induced proliferation of HUASMCs and increased the expression levels of cyclins A and D1. Knocking down either cyclin A or cyclin D1 by small interfering RNA (siRNA) inhibited homocysteine-induced cell proliferation. Furthermore, treatment with extracellular signal-related kinase (ERK) inhibitor (PD98059) and dominant negative Ras (RasN17) abolished homocysteine-induced cyclin A expression; and treatment with phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) and mammalian target of rapamycin (mTOR) inhibitor (rapamycin) attenuated the homocysteine-induced cyclin D1 expression. Homocysteine also induced transient phosphorylation of ERK, Akt, and p70 ribosomal S6 kinase (p70S6K). Neutralizing antibody and siRNA for beta 1 integrin blocked cell proliferation, expression of cyclins A and D1, and phosphorylation of ERK and Akt. In conclusion, homocysteine-induced differential activation of Ras/ERK and PI3K/Akt/p70S6K signaling pathways and consequent expression of cyclins A and D1 are dependent on beta 1 integrin. Homocysteine may accelerate progression of atherosclerotic lesions by promoting SMC proliferation. J. Cell. Physiol. 226: 1017-1026, 2011. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:1017 / 1026
页数:10
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