PCBP2 siRNA reverses the alcohol-induced pro-fibrogenic effects in hepatic stellate cells

Ravi S. Shukla, Bin Qin, Yu-Jui Yvonne Wan, Kun Cheng

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Purpose: Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP 2), encoded by the poly(rC) binding protein 2 (PCBP2) gene, binds to the 3′ end of the collagen mRNA and increases its half-life. This study aimed to reverse the pro-fibrogenic effect of alcohol on hepatic stellate cells (HSCs) by silencing the PCBP2 gene with siRNA. Methods: The silencing effects of a series of predesigned PCBP2 siRNAs were evaluated in the rat hepatic stellate cell line, HSC-T6. The pro-fibrogenic effects of alcohol on the expression levels of PCBP2 and type-I collagen were examined by several methods. The effect of PCBP2 siRNA on the stability of type I collagen α1(I) mRNA was investigated by an in vitro mRNA decay assay. Results: We identified one potent PCBP2 siRNA that reversed the alcohol-induced expression of PCBP2 in HSCs. The decay rate of the collagen α1(I) mRNA increased significantly in HSCs treated with the PCBP2 siRNA. Conclusion: This study provides the first evidence that alcohol up-regulates the expression of PCBP2, which subsequently increases the half-life of collagen α1(I) mRNA. Silencing of PCBP2 using siRNA may provide a promising strategy to reverse the alcohol-induced pro-fibrogenic effects in HSCs.

Original languageEnglish (US)
Pages (from-to)3058-3068
Number of pages11
JournalPharmaceutical Research
Volume28
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Keywords

  • alcoholic liver fibrosis
  • mRNA stability
  • PCBP2
  • siRNA
  • type I collagen

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Organic Chemistry
  • Molecular Medicine
  • Pharmacology (medical)
  • Biotechnology
  • Pharmacology

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