首页> 外文期刊>American Journal of Physiology >Follistatin attenuates early liver fibrosis: effects on hepatic stellate cell activation and hepatocyte apoptosis.
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Follistatin attenuates early liver fibrosis: effects on hepatic stellate cell activation and hepatocyte apoptosis.

机译:卵泡抑素可减轻早期肝纤维化:对肝星状细胞活化和肝细胞凋亡的影响。

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Activin A, a member of the transforming growth factor-beta superfamily, is constitutively expressed in hepatocytes and regulates liver mass through tonic inhibition of hepatocyte DNA synthesis. Follistatin is the main biological inhibitor of activin bioactivity. These molecules may be involved in hepatic fibrogenesis, although defined roles remain unclear. We studied activin and follistatin gene and protein expression in cultured rat hepatic stellate cells (HSCs) and in rats given CCl4 for 8 wk and examined the effect of follistatin administration on the development of hepatic fibrosis. In activated HSCs, activin mRNA was upregulated with high expression levels, whereas follistatin mRNA expression was unchanged from baseline. Activin A expression in normal lobular hepatocytes redistributed to periseptal hepatocytes and smooth muscle actin-positive HSCs in the fibrotic liver. A 32% reduction in fibrosis, maximal at week 4, occurred in CCl4-exposed rats treated with follistatin. Hepatocyte apoptosis decreased by 87% and was maximal at week 4 during follistatin treatment. In conclusion, activin is produced by activated HSCs in vitro and in vivo. Absence of simultaneous upregulation of follistatin gene expression in HSCs suggests that HSC-derived activin is biologically active and unopposed by follistatin. Our in vivo and in vitro results demonstrate that activin-mediated events contribute to hepatic fibrogenesis and that follistatin attenuates early events in fibrogenesis by constraining HSC proliferation and inhibiting hepatocyte apoptosis.
机译:活化素A是转化生长因子β超家族的成员,在肝细胞中组成性表达,并通过抑制肝细胞DNA合成来调节肝脏质量。卵泡抑素是激活素生物活性的主要生物抑制剂。这些分子可能参与肝纤维化,尽管尚不清楚明确的作用。我们研究了培养的大鼠肝星状细胞(HSCs)和给予CCl4的大鼠在8周内的激活素,卵泡抑素基因和蛋白质表达,并研究了卵泡抑素给药对肝纤维化发展的影响。在激活的HSC中,激活素mRNA以高表达水平上调,而卵泡抑素mRNA表达与基线相比没有变化。正常小叶肝细胞中的激活素A表达重新分布于纤维化肝脏中的中隔肝细胞和平滑肌肌动蛋白阳性HSC。接受卵泡抑素治疗的CCl4暴露大鼠的纤维化减少32%,最大于第4周。卵泡抑素治疗期间,肝细胞凋亡减少了87%,在第4周达到最大。总之,激活素是由激活的HSC在体外和体内产生的。在HSC中不存在同时上调卵泡抑素基因表达的现象提示,HSC衍生的激活素具有生物学活性并且不受卵泡抑素的反对。我们的体内和体外结果表明,激活素介导的事件有助于肝纤维化,而卵泡抑素可通过抑制HSC增殖并抑制肝细胞凋亡来减弱纤维发生的早期事件。

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