microRNA-143-3p attenuated development of hepatic fibrosis in autoimmune hepatitis through regulation of TAK1 phosphorylation
| Autor: | Yong-Ping Chen, Qianjing Du, Xiao-Dong Wang, Yuedong Xu, Lanman Xu, Tongtong Pan, Dazhi Chen, Chao Cai, Hanxiao Tu, Teng Teng, Hongwei Lin, Lina Sheng, Rui Wang, Jingjing Tu, Zhuo Lin |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Genetic enhancement TAK1 Inflammation Autoimmune hepatitis Chronic liver disease 03 medical and health sciences Mice 0302 clinical medicine Fibrosis Medicine Animals liver fibrosis Liver injury autoimmune hepatitis business.industry Cell Biology Original Articles medicine.disease MAP Kinase Kinase Kinases gene therapy miR‐143 Hepatitis Autoimmune MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Hepatocyte Cancer research Hepatocytes Molecular Medicine Original Article medicine.symptom business Hepatic fibrosis |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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