MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2

• Published in: World journal of gastroenterology : WJG Vol. 25; no. 31; pp. 4468 - 4480
• Main Authors: Wu, Jun-Cheng, Chen, Rong, Luo, Xin, Li, Zheng-Hong, Luo, Sheng-Zheng, Xu, Ming-Yi
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Inc 21.08.2019
• Subjects: Animals; Basic Study; Carbon Tetrachloride - toxicity; Cell Line; Cell Proliferation - genetics; Cohort Studies; Down-Regulation; G1 Phase Cell Cycle Checkpoints - genetics; Hepatic Stellate Cells - pathology; Humans; Liver - cytology; Liver - drug effects; Liver - pathology; Liver Cirrhosis, Experimental - chemically induced; Liver Cirrhosis, Experimental - genetics; Liver Cirrhosis, Experimental - pathology; Male; Mice; MicroRNAs - agonists; MicroRNAs - genetics; MicroRNAs - metabolism; Proto-Oncogene Proteins c-akt - genetics; RNA, Small Interfering - metabolism; Signal Transduction - genetics; MicroRNA-194; Hepatic stellate cells; Liver fibrosis; AKT2
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v25.i31.4468

Activation of hepatic stellate cells (HSCs) is a pivotal event in the onset and progression of liver fibrosis. Loss of microRNA-194 (miR-194) has been reported in activated HSCs, but the actual role of miR-194 in liver fibrosis remains uncertain. To explore the role and potential mechanism of miR-194-mediated regulation of liver fibrosis and . The expression of miR-194 was examined in human fibrotic liver tissues, activated HSCs, and a carbon tetrachloride (CCl ) mouse model by qPCR. The effects of AKT2 regulation by miR-194 on the activation and proliferation of HSCs were assessed . For experiments, we reintroduced miR-194 in mice using a miR-194 agomir to investigate the functions of miR-194 in liver fibrosis. MiR-194 expression was notably lacking in activated HSCs from both humans and mice. Overexpression of miR-194 (OV-miR-194) inhibited α-smooth muscle actin (α-SMA) and type I collagen (Col I) expression and suppressed cell proliferation in HSCs by causing cell cycle arrest in G0/G1 phase. AKT2 was predicted to be a target of miR-194. Notably, the effects of miR-194 knockdown in HSCs were almost blocked by AKT2 deletion, indicating that miR-194 plays a role in HSCs regulation of AKT2. Finally, miR-194 agomir treatment dramatically ameliorated liver fibrosis in CCl -treated mice. We revealed that miR-194 plays a protective role by inhibiting the activation and proliferation of HSCs AKT2 suppression. Our results further propose miR-194 as a potential therapeutic target for liver fibrosis.