Inhibition of pro-collagen I expression by oxymatrine in hepatic stellate cells is mediated via nuclear translocation of Y-box binding protein 1
Inhibition of pro-collagen I expression by oxymatrine in hepatic stellate cells is mediated via nuclear translocation of Y-box binding protein 1
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DOI：
10.3892/mmr.2015.4428
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发表时间：
2015-12-01
影响因子：
3.4
通讯作者：
Liu, Fei
中科院分区：
文献类型：
--
作者：
Du, Meiling;Zhang, Jun;Liu, Fei
氧化苦参碱（oxymatrine，OMT）是一种从中药苦参中提取的生物碱类化合物，具有抗肝纤维化活性。本研究试图探讨OMT介导的抑制胶原生成的潜在机制。为此，用OMT（240、480或960 mg/l）处理LX-2人肝星状细胞系3-5天。OMT以剂量和时间依赖性方式降低I型前胶原的内源性表达，并伴随着重要转录因子Y盒结合蛋白1（YB-1）的下调，特别是在与高浓度OMT孵育的第四天。为了进一步探索细胞内YB-1水平的变化，分别提取细胞核/细胞质蛋白，随后的蛋白质印迹分析显示细胞核中YB-1的显著上调与细胞质中的下调平行，表明OMT处理诱导的YB-1核转位。在另一个实验中，使用小干扰RNA敲低YB-1导致I型胶原mRNA水平升高，从而逆转OMT治疗的效果。因此，本研究提示OMT对Ⅰ型前胶原表达的抑制作用在一定程度上是通过YB-1的核转位介导的。
Accumulating evidence indicated that oxymatrine (OMT), an alkaloid compound from the Chinese medicinal herb Sophora flavescens, exhibits activity against hepatic fibrosis. The present study attempted to explore the underlying mechanisms of OMT-mediated inhibition of collagen production. For this, the LX-2 human hepatic stellate cell line was treated with OMT (240, 480 or 960 mg/l) for 3-5 days. The endogenic expression of pro-collagen I was decreased by OMT in a dose- and time-dependent manner, accompanied with the downregulation of Y-box binding protein 1 (YB-1), a vital transcription factor, particularly on the fourth day of incubation with a high concentration of OMT. To further explore the intracellular changes in YB-1 levels, nuclear/cytoplasmic proteins were extracted separately, and subsequent western blot analysis revealed a significant upregulation of YB-1 in the nucleus in parallel with its downregulation in the cytoplasm, indicating the nuclear translocation of YB-1 induced by OMT treatment. In another experiment, knockdown of YB-1 using small interfering RNA led to elevated mRNA levels of collagen I, thereby reversing the effects of OMT treatment. In conclusion, these present study suggested that the attenuation of pro-collagen I expression caused by OMT was, to a certain extent, mediated via nuclear translocation of YB-1.