Curcumin affects β-catenin pathway in hepatic stellate cell in vitro and in vivo
Curcumin affects β-catenin pathway in hepatic stellate cell in vitro and in vivo
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DOI：
10.1111/jphp.12283
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发表时间：
2014-11-01
影响因子：
3.3
通讯作者：
Zhu, Huixia
中科院分区：
文献类型：
--
作者：
Cui, Lei;Jia, Xin;Zhu, Huixia
新的证据表明，Wnt/-catenin通路与包括肝纤维化在内的不同器官的纤维化有关。-Catenin促进肝星状细胞（HSCs）活化，这是肝纤维化发展的关键事件，并已成为一种新的纤维化介质。姜黄素是一种从姜黄中提取的天然活性成分，对肝纤维化具有抑制作用。本研究旨在研究姜黄素是否影响造血干细胞中-catenin的表达/活性，并探讨其潜在机制。方法采用Western blot、real-time PCR、转染法和电泳迁移量转移法，采用培养的造血干细胞和大鼠肝损伤模型。结果表明，姜黄素在体外和体内均可降低-catenin蛋白水平。姜黄素抑制-catenin的活化活性和dna结合活性。姜黄素处理降低了细胞核catenin蛋白水平。进一步的实验表明，δ样同源物1有助于姜黄素抑制培养hsc中-catenin的反活化活性。结论姜黄素影响HSC -catenin通路，可能为姜黄素对HSC活化和肝纤维化的影响提供了新的解释。
ObjectivesEmerging evidence indicates that Wnt/-catenin pathway is linked to the fibrosis of different organs including liver fibrosis. -Catenin promotes hepatic stellate cells (HSCs) activation, a key event in the development of liver fibrosis, and has emerged as a novel mediator of fibrosis. Curcumin, a natural active ingredient derived from turmeric, possesses an inhibitory effect on liver fibrosis. This study is aimed to examine whether curcumin affects -catenin expression/activity in HSCs and explores the underlying mechanisms.MethodsThe researchers used Western blot, real-time PCR, transfection assay and electrophoretic mobility shift assay and employed cultured HSCs and rat model of liver injury.Key findingsResults showed that curcumin could reduce -catenin protein level in HSCsin vitro and in vivo. Both -catenin transactivation activity and DNA-binding activity were suppressed by curcumin. Moreover, nuclear -catenin protein level was decreased by curcumin treatment. Further experiments suggested that delta-like homologue 1 contributed to curcumin inhibition of -catenin transactivation activity in cultured HSCs.ConclusionsCurcumin affects -catenin pathway in HSCs and might suggest a possible new explanation for the effects of curcumin on HSC activation and liver fibrosis.