| First Author | Wu JC | Year | 2019 |
| Journal | World J Gastroenterol | Volume | 25 |
| Issue | 31 | Pages | 4468-4480 |
| PubMed ID | 31496625 | Mgi Jnum | J:290462 |
| Mgi Id | MGI:6435382 | Doi | 10.3748/wjg.v25.i31.4468 |
| Citation | Wu JC, et al. (2019) MicroRNA-194 inactivates hepatic stellate cells and alleviates liver fibrosis by inhibiting AKT2. World J Gastroenterol 25(31):4468-4480 |
| abstractText | BACKGROUND: 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. AIM: To explore the role and potential mechanism of miR-194-mediated regulation of liver fibrosis in vitro and in vivo. METHODS: The expression of miR-194 was examined in human fibrotic liver tissues, activated HSCs, and a carbon tetrachloride (CCl4) mouse model by qPCR. The effects of AKT2 regulation by miR-194 on the activation and proliferation of HSCs were assessed in vitro. For in vivo experiments, we reintroduced miR-194 in mice using a miR-194 agomir to investigate the functions of miR-194 in liver fibrosis. RESULTS: MiR-194 expression was notably lacking in activated HSCs from both humans and mice. Overexpression of miR-194 (OV-miR-194) inhibited alpha-smooth muscle actin (alpha-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 via regulation of AKT2. Finally, miR-194 agomir treatment dramatically ameliorated liver fibrosis in CCl4-treated mice. CONCLUSION: We revealed that miR-194 plays a protective role by inhibiting the activation and proliferation of HSCs via AKT2 suppression. Our results further propose miR-194 as a potential therapeutic target for liver fibrosis. |
