Effect of reversine on cell cycle, apoptosis, and activation of hepatic stellate cells
Effect of reversine on cell cycle, apoptosis, and activation of hepatic stellate cells
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DOI：
10.1007/s11010-016-2815-x
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发表时间：
2016-12-01
影响因子：
4.3
通讯作者：
Gu, Weili
中科院分区：
文献类型：
--
作者：
Huang, Yu;Huang, Di;Gu, Weili
实验和临床证据表明肝纤维化具有潜在的可逆性。肝星状细胞（HSCs）在肝纤维化的发展中起着关键作用。有研究表明，逆转录酶可诱导细胞凋亡。我们试图阐明逆转录酶对细胞周期、凋亡和造血干细胞活化的影响。数据显示，逆转诱导hsc形态学改变，抑制细胞增殖，诱导细胞周期阻滞在G2/M期。逆转通过caspase依赖性和线粒体依赖性途径诱导细胞凋亡。逆转素通过tgf - β信号通路和降解细胞外基质蛋白胶原- 1抑制hsc的活化。TIMP1和tgf - β(1)蛋白的降低促进了纤维化的逆转。由于在体外可诱导造血干细胞凋亡，抑制细胞增殖，降低造血干细胞活化，降解细胞外基质，逆转肝纤维化可能是一种很有前景的药物。
Experimental and clinical evidence show that liver fibrosis is potentially reversible. Hepatic stellate cells (HSCs) play a key role in the development of liver fibrosis. Some studies have shown that reversine could induce cell apoptosis. We attempted to elucidate the effect of reversine on cell cycle, apoptosis, and activation of HSCs. Data showed that reversine induced morphological changes in HSCs, inhibited cell proliferation, and induced cell-cycle arrest at the G2/M phase. Reversine induced cell apoptosis through caspase-dependent and mitochondria-dependent pathways. Reversine inhibited the activation of HSCs through TGF-beta signaling pathway and degraded extracellular matrix protein collagen-I. The decreased TIMP1 and TGF-beta(1) proteins promoted fibrosis reversion. Reversine might be a promising drug for liver fibrosis reversion because it induces HSCs apoptosis, restrains cell proliferation, reduces HSCs activation, and degrades extracellular matrix in vitro.