MiR-706通过TAOK1信号通路抑制小鼠肝纤维化

MiR-706 inhibits mouse liver fibrosis through targeting TAOK1 signaling pathway

目的探讨mi R-706介导的TAOK1信号通路在小鼠肝纤维化进程中的作用及分子生物学机制。方法将C57BL/6小鼠随机分为胆总管结扎(bile duct ligation,BDL)肝纤维化模型组(BDL组)和假手术组两组,小鼠造模4周后取材,HE、Masson染色及Western blot分析检测小鼠肝纤维化造模是否成功;Real-time PCR检测肝组织内mi R-706的表达含量;免疫组织化学染色检测肝组织内TAOK1和TAOK1下游促使肝纤维化发生的MAPK通路相关基因的蛋白表达含量的变化。结果 HE及Masson染色显示胆总管结扎肝纤维化模型组中纤维间隔增多,同时,Western blot显示BDL组中α-SMA及collagen I含量增加,说明肝纤维化造模成功;Real-time PCR显示BDL组中mi R-706含量显著下降,同时,免疫组织化学染色显示,BDL组中TAOK1和其下游MAPK通路中P38与MEK3免疫反应性明显增强。结论肝纤维化组中可能由于mi R-706表达的下调,mi R-706对其下游TAOK1信号通路加重小鼠BDL所导致的肝纤维化进程。

Objective To investigate the role and molecular mechanism of mi R-706 in the process of mouse liver fibrosis through regulating TAOK1 signaling pathway. Methods C57 BL/6 mice were randomly divided into two groups： bile duct ligation group（BDL） and sham operation group. Mice were sacrificed 4 weeks after operation. HE, Masson staining and Western blot were used to evaluate the extend of liver fibrosis. The expression of mi R-706 in liver tissues was quantified by real-time PCR, while TAOK1 and MAPK pathway related gene expression were detected by immunohistochemistry. Results HE and Masson staining results showed increased scar tissues in BDL model group, while Western Blot indicated increased expression of α-SMA and Collagen I in BDL model group, together suggesting a hepatic fibrosis model was successfully established. Compared to control mice, mi R-706 level significantly decreased, while TAOK1 expression increased（P〈0.01） and downstream MAPK pathway was activated in BDL model group. Conclusion mi R-706 may play an important role in the process of mouse liver fibrosis by activating the TAOK1 signaling pathway.