Skip to main content
Silencing of α-complex protein-2 reverses alcohol- and cytokine-induced fibrogenesis in hepatic stellate cells
Published Web Location
https://pubmed.ncbi.nlm.nih.gov/28966795/No data is associated with this publication.
Abstract
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 investigated 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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.