Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin

IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. beta-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced beta-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of beta-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while beta-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of beta-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of beta-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of beta-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and beta-catenin pathway.