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.
Original language | English (US) |
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Pages (from-to) | 70-79 |
Number of pages | 10 |
Journal | Liver Research |
Volume | 1 |
Issue number | 1 |
DOIs | |
State | Published - Jun 2017 |
Keywords
- Epidermal growth factor (EGF)
- Hepatic stellate cells
- Liver fibrosis
- LY2a09761
- Migration
- Myofibroblast
- Platelet-derived growth factor (PDGF)
- Poly (rC) binding protein (PCBP)2
- Primary HSC
- Transforming growth factor(TGF)-β
ASJC Scopus subject areas
- Gastroenterology
- Hepatology