Background and aim:α-complex protein-2(αCP2)encoded by the poly(rC)binding protein 2(PCBP2)gene is responsible for the accumulation of type Ⅰ collagen in fibrotic livers.In this study,we silenced the PCBP2 gene using a small interfering RNA(siRNA)to reverse alcohol-and cytokine-induced profibrogenic effects on hepatic stellate cells(HSCs). Methods:Primary rat HSCs and the HSC-T6 cell line were used as fibrogenic models to mimic the initiation and perpetuation stages of fibrogenesis,respectively.We previously found that a PCBP2 siRNA,which efficiently silences expression of αCP2,reduces the stability of type Ⅰ collagen mRNA.We inves-tigated the effects of the PCBP2 siRNA on cell proliferation and migration.Expression of type Ⅰ collagen in HSCs was analyzed by quantitative real-time PCR and western blotting.In addition,we evaluated the effects of the PCBP2 siRNA on apoptosis and the cell cycle. Results:PCBP2 siRNA reversed multiple alcohol-and cytokine-induced profibrogenic effects on primary rat HSCs and HSC-T6 cells.The PCBP2 siRNA also reversed alcohol-and cytokine-induced accumulation of type Ⅰ collagen as well as cell proliferation and migration.Moreover,the combination of LY2109761,a transforming growth factor-β1 inhibitor,and the PCBP2 siRNA exerted a synergistic inhibitive effect on the accumulation of type Ⅰ collagen in HSCs. Conclusions:Silencing of PCBP2 using siRNA could be a potential therapeutic strategy for alcoholic liver fibrosis.