Icariin‐induced miR‐875‐5p attenuates epithelial‐mesenchymal transition by targeting hedgehog signaling in liver fibrosis. Issue 3 (7th November 2019)

• Record Type: Journal Article
• Authors: Ye, Lei; Yu, Yaping; Zhao, Yanping
• Is Part Of: Journal of gastroenterology and hepatology. Volume 35:Issue 3(2020)
• Page Start: 482
• Page End: 491
• Publication Date: 2019-11-07
• Subjects: GLI1 -- Icariin -- liver cirrhosis -- liver fibrosis -- miR‐875‐5p; Gastroenterology -- Periodicals; Digestive organs -- Diseases -- Periodicals; Liver -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Liver Diseases -- Periodicals; 616.33
• DOI: 10.1111/jgh.14875
• Languages: English
• ISSNs: 0815-9319

Abstract

Abstract: Background: Hepatic fibrosis is the final endpoint for most chronic liver diseases and remains a significant public health problem worldwide. Icariin, a naturally occurring flavonol glucoside, has been reported to exhibit protective effects on liver injury and alleviate liver fibrosis. However, the underlying detail molecular mechanism is not fully revealed. Methods: Mouse primary hepatic stellate cells (HSCs) and carbon tetrachloride (CCL4 )‐induced liver fibrosis model in mice were used as in vitro and in vivo models in this study. The expression levels of miR‐875‐5p were detected by quantitative reverse transcription‐PCR. The validation of the direct target of miR‐875‐5p was through dual‐luciferase reporter assay and western blotting assay. The cell proliferation and cell mobility were determined using MTT assay and Transwell migration assay, respectively. Results: We found that icariin inhibited epithelial–mesenchymal transition and collagen protein section of HSCs. Icariin exerted hepatoprotective effects on mice model of CCL4 ‐induced liver fibrosis. Our further results revealed that miR‐875‐5p was downregulated in human cirrhosis tissues and activated murine HSCs. Icariin induced miR‐875‐5p upregulation and subsequently decreased glioma‐associated oncogene homolog 1 (GLI1) expression through direct binding to the three prime untranslated region of GLI1 mRNA. Conclusion: Our study highlighted the potential therapeutic application of icariin for liver fibrosis management.