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

摘要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 inves-tigated 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.

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作者 Hao Liu [1] Zhijin Chen [1] Wei Jin [1] Ashutosh Barve [1] Yu-Jui Yvonne Wan [2] Kun Cheng [1] 学术成果认领
作者单位 Division of Pharmaceutical Sciences,School of Pharmacy,University of Missouri-Kansas City,Kansas City,MO,USA [1] Department of Pathology and Laboratory Medicine,UC Davis Medical Center,Sacramento,CA,USA [2]
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DOI 10.1016/j.livres.2017.05.003
发布时间 2024-05-06(万方平台首次上网日期,不代表论文的发表时间)
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肝脏研究(英文)

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