Silencing ofα-complex protein-2 reverses alcohol-and cytokine-induced fibrogenesis in hepatic stellate cells  

作　　者：Hao Liu Zhijin Chen Wei Jin Ashutosh Barve Yu-Jui Yvonne Wan Kun Cheng 

机构地区：[1]Division of Pharmaceutical Sciences,School of Pharmacy,University of Missouri-Kansas City,Kansas City,MO,USA [2]Department of Pathology and Laboratory Medicine,UC Davis Medical Center,Sacramento,CA,USA

出　　处：《Liver Research》2017年第1期70-79,共10页肝脏研究（英文）

基　　金：This work was supported by an award(1R01AA021510)from the National Institutes of Health.

摘　　要：Background and aim:a-complex protein-2(aCP2)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 aCP2,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-b1 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.

关 键 词：Hepatic stellate cells Primary HSC MYOFIBROBLAST Liver fibrosis Poly(rC)binding protein(PCBP)2 Transforming growth factor(TGF)-b Platelet-derived growth factor(PDGF) Epidermal growth factor(EGF) LY2a09761 Migration 

分 类 号：R73[医药卫生—肿瘤]