扶正化瘀片调控c-Jun/miR-27a/Wnt/β-catenin信号通路抑制肝星状细胞活化的抗肝纤维化机制研究

肝星状细胞（HSC）活化是肝纤维化发生发展中心环节。项目组证实扶正化瘀片及其主要成分丹参酮IIA有较好抗肝纤维化作用。miR-27a在肝硬化患者血清和活化HSC中高表达，为诊断肝硬化及HSC活化标志物；miR-27a靶向Wnt/β-catenin通路相关基因影响HSC活化；miR-27a促进c-Jun表达；c-Jun是miR-27a潜在转录因子，推测miR-27a、Wnt/β-catenin和c-Jun互相激活的环路在肝纤维化中有重要作用。扶正化瘀片下调肝硬化患者血清miR-27a表达；丹参酮IIA下调HSC中c-Jun和miR-27a表达。本项目在前期基础上，运用分子/细胞生物学及生物信息学等技术探明c-Jun/miR-27a/Wnt/β-catenin通路在HSC活化中分子机制，以此阐释扶正化瘀片治疗肝纤维化作用机理。此研究对肝纤维化诊断、形成机制和揭示中药机理研究，具有重要学术意义。

Hepatic stellate cells (HSC) are the main collagen-producing cells in the liver and their activation promotes liver fibrosis. We found that Fuzheng Huayu tablet and Tanshinone ⅡA alleviate liver fibrosis and inhibit the proliferation and activation of HSC. MiR-27a can be used as a predictor for the activation of HSC and the occurrence and development of liver cirrhosis. MiR-27a plays an important role in HSC activation by targeting the Wnt/β-catenin signaling pathway. MiR-27a promotes c-Jun expression and c-Jun may be a potential transcription factor for miR-27a by bioinformatics analysis, highlighting that c-Jun/miR-27a/Wnt/β-catenin signaling pathway may play an important role in HSC activation. We found that Fuzheng Huayu tablet exerts good effects against liver cirrhosis. MiR-27a was significantly downregulated in patients with liver cirrhosis by Fuzheng Huayu tablet. Tanshinone ⅡA is an active ingredient of Fuzheng Huayu tablet and downregulates the expression of c-Jun and miR-27a in HSC. Further study will investigate the molecular mechanism of the c-Jun/miR-27a/Wnt/β-catenin signaling pathway in HSC activation and the action mechanism of Fuzheng Huayu tablet against liver fibrosis. Elucidating the miR-27a-targets regulatory network may shed light on the molecular mechanism of liver fibrogenesis and may contribute to the diagnosis and treatment of liver fibrosis. It might help to elucidate the mechanism of traditional Chinese medicine for treating liver fibrosis.