miR-202 is a Promising Antifibrotic Therapeutic Target to Prevent Liver Fibrosis by Suppressing Gli3 In Vivo and In Vitro

摘要

Background: Liver fibrosis, a primary consequence of chronic liver injury, is characterized by the activation of hepatic stellate cells (HSCs) and the accumulation of extracellular matrix (ECM). Methods: The role of miR-202 and the interaction between miR-202 and Gli genes in liver fibrosis were determined. The interaction between Gli3 and miR-152 was evaluated by bioinformatic analysis and a dual-luciferase reporter assay. Results: The hydroxyproline content and the alpha-SMA expression were both elevated in liver tissues from rats with experimental liver fibrosis. The expression levels of alpha-SMA and albumin at the mRNA and protein levels were separately increased and decreased in LX2 cells. Moreover, miR-202 treatment in LX2 cells diminished alpha-SMA and Gli3 expression and promoted albumin expression. In addition, Gli3 was identified as a target gene of miR-202 by the luciferase reporter assay. Eventually, miR-202 treatment in the CCl4-induced rat model similarly reduced the alpha-SMA and Gli3 expression and augmented albumin expression. Moreover, it was further discovered that collagen deposition of liver tissues was obviously declined in the miR-202 group compared to that in the model group. Conclusion: Thus, these results implied that miR-202 might be protective against liver fibrosis via regulation of Gli3 and might be a promising target in the development of novel therapies to treat pathological fibrotic disorders.