The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis
The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis
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DOI：
10.1007/s00535-007-2020-5
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发表时间：
2007-06-01
影响因子：
6.3
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Jin, Haiyan;Terai, Shuii;Sakaida, Isao
背景肝星状细胞（hepatic stellate cells，HSC）在肝纤维化发生中起着重要作用。在这里，我们研究了铁螯合剂去铁胺（DFO）是否影响培养的HSC活化和凋亡。方法.使用静止和活化的星状细胞研究DFO对HSC的影响。结果用DFO处理抑制HSC活化，导致α-平滑肌肌动蛋白和I型前胶原、基质金属蛋白酶-2和-9以及金属蛋白酶组织抑制剂-1和-2 mRNA的表达减少。DFO诱导活化的HSC凋亡，这与Bcl-2表达降低和细胞色素c从线粒体释放到胞浆中以及caspase-3活性增强有关。DFO还诱导活化的HSC表达过氧化物酶体增殖物激活受体γ，并使细胞内脂质再积聚。结论.星状细胞的铁螯合抑制它们的活化，导致它们变得失活以及进行凋亡。这些数据表明铁螯合治疗肝纤维化的潜在作用。
Background. Hepatic stellate cells (HSCs) play a pivotal role in liver fibrogenesis. Here, we studied whether the iron chelator deferoxamine (DFO) affected cultured HSC activation and apoptosis. Methods. The effect of DFO on HSCs was investigated using quiescent and activated stellate cells. Results. Treatment with DFO inhibited HSC activation, resulting in the reduced expression of a-smooth muscle actin protein and type I procollagen, matrix metalloproteinase-2 and -9, and tissue inhibitors of metalloproteinase-1 and -2 mRNAs. DFO induced apoptosis of activated HSCs, which was associated with decreasing Bcl-2 expression and the release of cytochrome c from the mitochondria to the cytosol with enhanced caspase-3 activity. DFO also induced activated HSCs to express peroxisome proliferator-activated receptor gamma with the reaccumulation of intracellular lipids. Conclusions. The iron chelation of stellate cells inhibits their activation, causing them to become deactivated as well as to undergo apoptosis. These data suggest a potential role for an iron chelation treatment of liver fibrosis.