中国药理学通报Issue(1):37-42,6.DOI:10.3969/j.issn.1001-1978.2016.01.009
动脉平滑肌细胞 STIM1过表达上调Akt/mTOR 通路并促进细胞增殖
STIM1 promotes arterial smooth muscle cells proliferation by regulating Akt/mTOR pathway
摘要
Abstract
Aim To investigate the expression of stro-mal interaction molecule 1 (STIM1) in rat pulmonary arterial hypertension ( PAH ) tissues and effects of STIM1 on arterial muscle cells proliferation. Methods PAH was induced by a single intraperitoneal injec-tion of MCT at a dose of 60 mg·kg - 1 . The mRNA or protein expressions of STIM1 in monocrotaline-induced pulmonary hypertensive rats were measured by real-time PCR or Western blot, respectively. The arterial smooth muscle cells A7R5 were transiently transfected with STIM1 plasmids to prepare STIM1 overexpressed cells. Cell proliferations were detected by using CCK-8 kits. The expressions of Akt/ mTOR pathway molecules of A7R5 were measured by Western blot. Results The right ventricular systolic blood pressure ( RVSP) and right ventricular mass index ( RVMI ) were markedly elevated in MCT-treated rats (P < 0. 01) in comparison to control rats. The mRNA and protein ex-pression levels of STIM1 in monocrotaline-induced pul-monary hypertensive rats were 2. 19 and 1. 66 folds of control rats, respectively. STIM1 were transiently over-expressed in cultured A7R5. Cells transfected with STIM1 grew more quickly than non-transfected control. Overexpression of STIM1 significantly increased the phosphorylation of Akt, mTOR, p70-S6K, and 4E-BP1, but did not change their protein expression lev-els. Conclusion STIM1 are over-expressed in rat PAH tissues. Overexpression of STIM1 can promote ar-terial smooth muscle cells proliferation by regulating Akt/ mTOR pathway.关键词
肺动脉高压/动脉平滑肌细胞/基质相互作用分子1/细胞增殖/哺乳动物雷帕霉素靶蛋白/Akt 信号通路Key words
pulmonary hypertension/arterial smooth muscle cells/stromal interaction molecule 1 (STIM1)/cell proliferation/mammalian target of rapamycin (mTOR)/Akt signaling分类
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张明芳,齐元麟,王丹,王情,陈富华,林默君..动脉平滑肌细胞 STIM1过表达上调Akt/mTOR 通路并促进细胞增殖[J].中国药理学通报,2016,(1):37-42,6.基金项目
国家自然科学基金资助项目(No 31171104) (No 31171104)
福建省教育厅科技重点资助项目( No JA10130) ( No JA10130)
福建省自然科学基金资助项目(No 2015J01611,2013J01373) (No 2015J01611,2013J01373)