Homocysteine induces smooth muscle cell proliferation through differential regulation of cyclins A and D1 expression

Jui Kun Chiang, Mao Lin Sung, Hong Ren Yu, Hsin I. Chang, Hsing Chun Kuo, Tzung Chieh Tsai, Chia Kuang Yen, Cheng Nan Chen*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

37 引文 斯高帕斯(Scopus)

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 β1 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 β1 integrin. Homocysteine may accelerate progression of atherosclerotic lesions by promoting SMC proliferation.

原文英語
頁(從 - 到)1017-1026
頁數10
期刊Journal of Cellular Physiology
226
發行號4
DOIs
出版狀態已出版 - 04 2011

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