Abstract
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. β-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 β-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of β-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while β-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of β-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of β-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 β-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and β-catenin pathway.
Highlights
Both IL-22 and miRNA-200a alleviate the pathogenesis of liver fibrosis
Similar to the results of expression of miR-200a, we found that the liver fibrosis recovery slower after miR-200a inhibitor injection compared with PBS group and the IL-22 +miR-200a inhibitor group according to the Ishak fibrosis score (Fig. 7B)
In agreement with previous reports[3,4], our data showed that treatment with IL-22 significantly inhibited development of liver fibrosis
Summary
Both IL-22 and miRNA-200a alleviate the pathogenesis of liver fibrosis. Whether there is any crosstalk between IL-22 and miRNA-200a in anti-fibrotic effects remains unknown. We searched potential target of miR-200a and explored the mechanism of IL-22 and miR-200a in inhibiting HSC activity. We further examined the regulatory role of IL-22 in the expression of miR-200a and its target in a HSC cell line, primary HSCs and a rat model of liver fibrosis. Our results reveal the interaction between IL-22 and miR-200a in regulating the development of hepatic fibrosis
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