1. MiR-200c-3p targets SESN1 and represses the IL-6/AKT loop to prevent cholangiocyte activation and cholestatic liver fibrosis
- Author
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Yongfeng Song, Melanie Tran, Li Wang, Dong-Ju Shin, and Jianguo Wu
- Subjects
Liver Cirrhosis ,Cholestasis ,Interleukin-6 ,Sestrins ,Cell Cycle Proteins ,Cell Biology ,Pathology and Forensic Medicine ,Mice ,MicroRNAs ,Liver ,Animals ,Bile Ducts ,Proto-Oncogene Proteins c-akt ,Molecular Biology - Abstract
Cholestasis causes ductular reaction in the liver where the reactive cholangiocytes not only proliferate but also gain a neuroendocrine-like phenotype, leading to inflammatory cell infiltration and extracellular matrix deposition and contributing to the development and progression of cholestatic liver fibrosis. This study aims to elucidate the role of miR-200c in cholestasis-induced biliary liver fibrosis and cholangiocyte activation. We found that miR-200c was extremely abundant in cholangiocytes but was reduced by cholestasis in a bile duct ligation (BDL) mouse model; miR-200c was also decreased by bile acids in vitro. Phenotypically, loss of miR-200c exacerbated cholestatic liver injury, including periductular fibrosis, intrahepatic inflammation, and biliary hyperplasia in both the BDL model and the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) model. We identified sestrin 1 (SESN1) as a target of miR-200c. Sesn1
- Published
- 2022