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

Hao Liu, Zhijin Chen, Wei Jin, Ashutosh Barve, Yu Jui Yvonne Wan, Kun Cheng

Research output: Contribution to journalArticle

8 Scopus citations

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 languageEnglish (US)
Pages (from-to)70-79
Number of pages10
JournalLiver Research
Volume1
Issue number1
DOIs
StatePublished - 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

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