caa a22 4500 445312440 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0475-9 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0475-9 PCBP2 siRNA Reverses the Alcohol-induced Pro-fibrogenic Effects in Hepatic Stellate Cells [Elektronische Daten] [Ravi Shukla, Bin Qin, Yu-Jui Wan, Kun Cheng] ABSTRACT: Purpose: Type I collagen accumulates during liver fibrosis primarily because α-complex protein-2 (αCP2), 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. Springer Science+Business Media, LLC, 2011 alcoholic liver fibrosis nationallicence mRNA stability nationallicence PCBP2 nationallicence siRNA nationallicence type I collagen nationallicence Shukla Ravi Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut Qin Bin Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut Wan Yu-Jui Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, 66212, Kansas City, KS, USA aut Cheng Kun Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3058-3068 0724-8741 28:12<3058 2011 28 11095 https://doi.org/10.1007/s11095-011-0475-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0475-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shukla Ravi Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut NATIONALLICENCE 700 1- Qin Bin Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut NATIONALLICENCE 700 1- Wan Yu-Jui Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, 66212, Kansas City, KS, USA aut NATIONALLICENCE 700 1- Cheng Kun Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, 64108, Kansas City, MO, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3058-3068 0724-8741 28:12<3058 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer