title: PCBP2 siRNA reverses the alcohol-induced pro-fibrogenic effects in hepatic stellate cells.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Shukla
authors.forename: Bin
authors.initials: B
authors.lastname: Qin
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
authors.forename: Kun
authors.initials: K
authors.lastname: Cheng
mesh_terms: D000438:Alcohols / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism*; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000438:Alcohols; D024042:Collagen Type I; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C571107:poly(rC) binding protein 2, rat