Silencing of α-complex protein-2 reverses alcohol-and cytokine-induced fibrogenesis in hepatic stellate cells
10.1016/j.livres.2017.05.003
- Author:
Liu HAO
1
;
Chen ZHIJIN
;
Jin WEI
;
Barve ASHUTOSH
;
Wan Yvonne YU-JUI
;
Cheng KUN
Author Information
1. Division of Pharmaceutical Sciences
- Keywords:
Hepatic stellate cells;
Primary HSC;
Myofibroblast;
Liver fibrosis;
Poly(rC)binding protein(PCBP)2;
Transforming growth factor(TGF)-β;
Platelet-derived growth factor(PDGF);
Epidermal growth factor(EGF);
LY2a09761;
Migration
- From:
Liver Research
2017;1(1):70-79
- CountryChina
- Language:Chinese
-
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 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.
