piR-823在肝纤维化中通过翻译起始因子EIF3B启动TGF-β1翻译促进HSC活化

piRNA 是一类小分子非编码RNA，在肝脏表达丰富。其中一种piR-823在肝硬化、肝癌前病变、肝癌中表达异常。TGF-β1可活化肝星状细胞（HSC），是最重要的促肝纤维化细胞因子，EIF3B蛋白可调控TGF-β1的翻译。我们前期研究发现：活化的HSC中piR-823表达升高，过表达piR-823可促进HSC活化；RNA pull down及质谱分析发现，piR-823可与EIF3B结合。据此推测，piR-823可能通过与EIF3B结合促进TGF-β1翻译，进而活化HSC，促进肝纤维化。本项目拟在动物模型和HSC中观察肝纤维化中，HSC的 piR-823表达；过表达/敲低piR-823表达，观察其对HSC活化的调控作用；在整体水平过表达/敲低piR-823，证明其功能；并进一步验证piR-823与EIF3B结合促进TGF-β1翻译，明确其分子机制。本项目为阐明肝纤维化机制提供了新思路。

There are rich piRNAs in the liver which is one of the small non-coding RNA. Studies show that the expression of piR-823 is increased in liver cirrhosis and hepatocellular carcinoma compared to normal liver. TGF-β1 is the most important profibrotic factor for liver fibrosis which actives hepatic stellate cells (HSC). EIF3B is the translation initiation factor to start the translation of TGF-β1. In the previous study we found that the exprssion of piR-823 increased in activated HSC and it promoted the activation of HSC when the exprssion of piR-823 increased. Meanwhile piR-823 combined with EIF3B in HSC by using RNA pull down method and LC-MSMS. We speculate that piR-823 actives hepatic stellate cells through promoting TGF -β1 translation via conjuncting with EIF3B. We aim to clarify the changes of expression of piR-823 in HSC in the dynamic process of hepatic fibrosis and change the expression of piR-823 in HSC to investigate the activation of HSC. Finally explore the mechanisms of piR-823 activating HSC. It provides a new mechanism of hepatic fibrosis.