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Icariin‐induced miR‐875‐5p attenuates epithelial‐mesenchymal transition by targeting hedgehog signaling in liver fibrosis
Author(s) -
Ye Lei,
Yu Yaping,
Zhao Yanping
Publication year - 2020
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.14875
Subject(s) - hepatic stellate cell , icariin , gli1 , downregulation and upregulation , cancer research , epithelial–mesenchymal transition , medicine , hepatic fibrosis , fibrosis , cirrhosis , viability assay , hedgehog signaling pathway , oncogene , microbiology and biotechnology , cell , pathology , signal transduction , chemistry , biology , cell cycle , biochemistry , cancer , alternative medicine , gene
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 (CCL 4 )‐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 CCL 4 ‐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.