PCBP2 siRNA Reverses the Alcohol-induced Pro-fibrogenic Effects in Hepatic Stellate Cells

Type I collagen accumulates during liver fibrosis primarily because alpha-complex protein-2 (alpha CP(2)), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3' end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cells (HSCs) by silencing the PCBP2 gene with siRNA. The silencing effects of a series of predesigned PCBP2 siRNAs were evaluated in the rat hepatic stellate cell line, HSC-T6. The pro-fibrogenic effects of alcohol on the expression levels of PCBP2 and type-I collagen were examined by several methods. The effect of PCBP2 siRNA on the stability of type I collagen alpha 1(I) mRNA was investigated by an in vitro mRNA decay assay. We identified one potent PCBP2 siRNA that reversed the alcohol-induced expression of PCBP2 in HSCs. The decay rate of the collagen alpha 1(I) mRNA increased significantly in HSCs treated with the PCBP2 siRNA. This study provides the first evidence that alcohol up-regulates the expression of PCBP2, which subsequently increases the half-life of collagen alpha 1(I) mRNA. Silencing of PCBP2 using siRNA may provide a promising strategy to reverse the alcohol-induced pro-fibrogenic effects in HSCs.