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 Citations (Scopus)

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

Fingerprint

Hepatic Stellate Cells
Small Interfering RNA
Alcohols
Messenger RNA
Collagen Type I
Collagen
Half-Life
Genes
RNA Stability
Gene Silencing
Liver Cirrhosis
Liver
Rats
Assays
Carrier Proteins
Up-Regulation
Cell Line
Proteins

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

Cite this

PCBP2 siRNA reverses the alcohol-induced pro-fibrogenic effects in hepatic stellate cells. / Shukla, Ravi S.; Qin, Bin; Wan, Yu-Jui Yvonne; Cheng, Kun.

In: Pharmaceutical Research, Vol. 28, No. 12, 12.2011, p. 3058-3068.

Research output: Contribution to journalArticle

Shukla, Ravi S. ; Qin, Bin ; Wan, Yu-Jui Yvonne ; Cheng, Kun. / PCBP2 siRNA reverses the alcohol-induced pro-fibrogenic effects in hepatic stellate cells. In: Pharmaceutical Research. 2011 ; Vol. 28, No. 12. pp. 3058-3068.
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