microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation
microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation
复制标题
microRNA-143-3p通过调节TAK1磷酸化减轻自身免疫性肝炎肝纤维化的发展
DOI：
10.1111/jcmm.14750
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发表时间：
2019-12-06
影响因子：
5.3
通讯作者：
Chen, Yongping
中科院分区：
文献类型：
--
作者：
Tu, Hanxiao;Chen, Dazhi;Chen, Yongping
自身免疫性肝炎（Autoimmune hepatitis，AIH）是一种由自身免疫系统攻击肝细胞引起的慢性肝病。细胞内信号传导和miRNA可能在肝损伤的调控中发挥重要作用。本研究旨在探讨microRNA 143在小鼠AIH模型和肝细胞损伤模型中的潜在作用。用肝抗原S100诱导小鼠AIH模型，用脂多糖诱导小鼠肝细胞损伤模型。将小鼠和AML 12细胞分成6组，分别给予或不给予miRNA-143处理。通过不同的细胞和分子技术检测炎症和纤维化以及基因表达。模型成功建立，ALT和AST以及炎症和纤维化标志物升高。在小鼠或肝细胞中感染或转染mir-143显著减弱了肝细胞损伤减轻的发展。此外，该研究证明了TAK 1介导的miRNA-143的磷酸化调节肝脏炎症和纤维化以及肝细胞损伤。我们的研究证明了miRNA-143在减轻AIH小鼠和肝细胞肝损伤中的重要作用。miRNA-143通过调节TAK 1磷酸化来调节炎症和纤维化，这使得TAK 1成为开发自身免疫性肝炎新治疗策略的靶点。
Autoimmune hepatitis (AIH) is a chronic liver disease due to autoimmune system attacks hepatocytes and causes inflammation and fibrosis. Intracellular signalling and miRNA may play an important role in regulation of liver injury. This study aimed to investigate the potential roles of microRNA 143 in a murine AIH model and a hepatocyte injury model. Murine AIH model was induced by hepatic antigen S100, and hepatocyte injury model was induced by LPS. Mice and AML12 cells were separated into six groups with or without the treatment of miRNA‐143. Inflammation and fibrosis as well as gene expression were examined by different cellular and molecular techniques. The model was successfully established with the elevation of ALT and AST as well as inflammatory and fibrotic markers. Infection or transfection of mir‐143 in mice or hepatocytes significantly attenuated the development of alleviation of hepatocyte injury. Moreover, the study demonstrated phosphorylation of TAK1‐mediated miRNA‐143 regulation of hepatic inflammation and fibrosis as well as hepatocyte injury. Our studies demonstrated a significant role of miRNA‐143 in attenuation of liver injury in AIH mice and hepatocytes. miRNA‐143 regulates inflammation and fibrosis through its regulation of TAK1 phosphorylation, which warrants TAK1 as a target for the development of new therapeutic strategy of autoimmune hepatitis.