Icariin-induced miR-875-5p attenuates epithelial-mesenchymal transition by targeting hedgehog signaling in liver fibrosis.

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 qRT-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 3'-untranslated region (UTR) of GLI1 mRNA.

CONCLUSION: Our study highlighted the potential therapeutic application of icariin for liver fibrosis management.