Fluorofenidone alleviates liver fibrosis by inhibiting hepatic stellate cell autophagy via the TGF-β1/Smad pathway

Abstract

Abstract Objectives Liver fibrosis is a key stage in the progression of various chronic liver diseases to cirrhosis, but at present, there is no effective treatment. This study examined the therapeutic effect of the new antifibrotic drug Fluorofenidone (AKF-PD) on liver fibrosis and its related mechanism. Materials and methods The effects of AKF-PD on hepatic stellate cell (HSC) autophagy and extracellular matrix (ECM) expression were assessed in a carbon tetrachloride (CCl4)-induced rat liver fibrosis model. In vitro, HSC-T6 cells were transfected with Smad2 and Smad3 overexpression plasmids and treated with AKF-PD. The viability and number of autophagosomes in HSC-T6 cells were examined. Beclin-1, LC3 and P62 protein expression were analysed by Western blotting. Results AKF-PD attenuated liver injury and ECM production in CCl4-induced liver fibrosis. In vitro, the viability and the number of autophagosomes in HSCs were decreased significantly by AKF-PD treatment. In addition, the protein expression of FN, α-SMA, collagen III, Beclin-1 and LC3 was increased, and P62 expression was decreased by the overexpression of Smad2 and Smad3; however, AKF-PD reversed these effects. Conclusions AKF-PD alleviates liver fibrosis by inhibiting HSC autophagy via the transforming growth factor (TGF)-β1/Smad pathway.