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首页> 外文期刊>American Journal of Physiology >Concerted effect of transforming growth factor-beta, cyclin inhibitor p21, and c-myc on smooth muscle cell proliferation.
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Concerted effect of transforming growth factor-beta, cyclin inhibitor p21, and c-myc on smooth muscle cell proliferation.

机译：转化生长因子-β，细胞周期蛋白抑制剂p21和c-myc对平滑肌细胞增殖的协同作用。

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摘要

Increased aortic smooth muscle cell (SMC) proliferation is a key event in the pathogenesis of atherosclerosis. Transforming growth factor-beta (TGF-beta) is one of the potent inhibitors of SMC proliferation. The purpose of this study was 1) to explore the effect of TGF-beta inhibition on proliferation of SMC and expression of growth regulatory molecules like p21 and c-myc and 2) to determine whether restoration of cell cycle regulatory molecules normalizes the altered proliferation. To test the role of TGF-beta in SMC proliferation, using antisense plasmid DNA, we inhibited TGF-beta gene from aortic SMC, which resulted in a significant increase (P < 0.03) in proliferation (studied by quantifying new DNA synthesis with [(3)H]thymidine uptake assay). In TGF-beta-altered SMC (TASMC), the mRNA expression (studied by RT-PCR) of c-myc was increased whereas that of the cyclin inhibitor p21 was completely inhibited. Using p21 sense plasmid DNA, we transfected p21 gene in TASMC, which restored p21 mRNA and protein expression and decreased proliferation (P < 0.002) in TASMC. Similar treatment with c-myc antisense oligonucleotides significantly (P < 0.001) decreased the proliferation of TASMC. TASMC also exhibited alteration in morphological changes in SMC but returned to normal with treatment of p21 and TGF-beta sense plasmid DNA. Two-dimensional gel electrophoresis analysis of SMC and TASMC demonstrated differential expression of proteins relevant to cellular proliferation and atherosclerosis. This study uniquely analyzes the effect of TGF-beta at the molecular level on proliferation of SMC and on cell cycle regulatory molecules, implicating their potential role in the pathogenesis of atherosclerosis.
机译：主动脉平滑肌细胞（SMC）增殖增加是动脉粥样硬化发病机理中的关键事件。转化生长因子-β（TGF-β）是SMC增殖的有效抑制剂之一。这项研究的目的是1）探索TGF-β抑制作用对SMC增殖和生长调节分子（如p21和c-myc）表达的影响，以及2）确定细胞周期调节分子的恢复是否能使改变的增殖正常化。为了测试TGF-β在SMC增殖中的作用，我们使用了反义质粒DNA，我们抑制了来自主动脉SMC的TGF-β基因，从而导致增殖显着增加（P <0.03）（通过用[[ 3）H]胸苷摄取测定）。在TGF-β改变的SMC（TASMC）中，c-myc的mRNA表达（通过RT-PCR研究）增加，而细胞周期蛋白抑制剂p21的mRNA表达被完全抑制。使用p21有义质粒DNA，我们转染了TASMC中的p21基因，其恢复了p21 mRNA和蛋白质表达并减少了TASMC中的增殖（P <0.002）。用c-myc反义寡核苷酸进行的相似处理显着（P <0.001）降低了TASMC的增殖。 TASMC也表现出SMC形态改变的改变，但通过p21和TGF-β有义质粒DNA的治疗恢复了正常。 SMC和TASMC的二维凝胶电泳分析表明与细胞增殖和动脉粥样硬化有关的蛋白质的差异表达。这项研究独特地分析了TGF-β在分子水平上对SMC增殖和细胞周期调节分子的影响，暗示了它们在动脉粥样硬化发病机理中的潜在作用。

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