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丙型肝炎病毒核心蛋白下调沉默信息调节因子1导致肝星状细胞活化 预览

Hepatitis C virus core protein induces activation of hepatic stellate cell by down-regulation of silent information regulator 1
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摘要 目的研究丙型肝炎病毒(HCV)核心蛋白对肝星状细胞沉默信息调节因子1(SIRT1)表达及肝星状细胞活化的影响。方法 HepG2细胞或表达HCV核心蛋白的HepG2细胞与肝星状细胞(LX-2细胞)共培养。应用液体闪烁计数仪、实时荧光定量-PCR、Western印迹检测LX-2细胞SIRT1活性、mRNA及蛋白的表达。Western印迹检测LX-2细胞磷酸化AMP激活的蛋白激酶(p-AMPK)、脂联素受体2(AdipoR2)、转化生长因子-β1(TGF-β1)蛋白的表达。ELISA法检测共培养上清液中人Ⅳ胶原(ColⅣ)、Ⅲ型前胶原肽(PⅢNP)、透明质酸(HA)和人层黏连蛋白(LN)的水平。计量资料采用t检验。结果与LX-2细胞和HepG2细胞共培养组相比,LX-2细胞和表达HCV核心蛋白HepG2细胞共培养组SIRT1活性(0.4±0.1比1.0±0.2,t=6.573,P〈0.01)、mRNA(0.3±0.1比1.0±0.3,t=5.422,P〈0.01)和蛋白(0.4±0.1比0.8±0.2,t=4.382,P〈0.01)水平下降;p-AMPK(0.3±0.1比0.8±0.2,t=5.477,P〈0.01)和AdipoR2(0.4±0.1比0.8±0.2,t=4.382,P〈0.01)表达下降;TGF-β1(2.3±0.5比0.8±0.2,t=6.823,P〈0.01)表达增加;共培养上清液中ColⅣ、PⅢNP、HA和LN的水平增加。SIRT1激动剂白藜芦醇降低TGF-β1的表达。结论 HCV核心蛋白下调肝星状细胞SIRT1活性及表达,下调AdipoR2表达,上调TGF-βl表达,活化肝星状细胞。 Objective To investigate the effects of hepatitis C virus(HCV)core protein on expression of silent information regulator 1(SIRT1)and activation of hepatic stellate cells(HSC).Methods HSC(LX-2 cells)were cocultured with HepG2 cells or HCV core protein-positive HepG2 cells.Activity,mRNA and protein expressions of SIRT1 in LX-2 cells were detected using scintillation counter,real time-PCR(RT-PCR)and western blot,respectively.Expressions of phosphorylated adenosine monophosphate activated protein kinase(p-AMPK),adiponectin receptor 2(AdipoR2)and transforming growth factorβ1(TGF-β1)were measured using western blot.Levels of collagenⅣ(ColⅣ),procollagenⅢpeptide(P Ⅲ NP),hyaluronan(HA)and laminin(LN)in the supernatant were measured using enzyme-linked immunosorbent assay(ELISA).The quantitative data was analyzed using t-test.Results Compared with LX-2 cells cocultured with HepG2 cells,the activity(0.4±0.1 vs.1.0±0.2,t=6.573,P<0.01),mRNA(0.3±0.1 vs.1.0±0.3,t=5.422,P<0.01)and protein expressions(0.4±0.1 vs.0.8±0.2,t=4.382,P<0.01)of SIRT1 were both reduced in LX-2 cells co-cultured with HCV core-positive HepG2 cells.In LX-2 cells co-cultured with HCV core-positive HepG2 cells,the expression levels of p-AMPK protein(0.3±0.1 vs.0.8±0.2,t=5.477,P<0.01)and AdipoR2 protein(0.4±0.1vs.0.8±0.2,t=4.382,P<0.01)were decreased comparing with those in LX-2 cells co-cultured with HepG2 cells,while TGF-β1 protein expression(2.3±0.5 vs 0.8±0.2,t=6.823,P<0.01)was increased.Moreover,the levels of ColⅣ,PⅢNP,HA and LN in the supernatant were increased in LX-2 cells co-cultured with HCV core-positive HepG2 cells.SIRT1 activator resveratrol decreased the expression of TGF-β1 protein.Conclusion HCV core protein might decrease the expression of AdipoR2 and increase the expression of TGF-β1 through down-regulating the activity and expression of SIRT1,and ultimately cause the activation of HSC.
作者 孙丽杰 施宇光 张晓宇 舒梦妮 陈墨洋 于建武 SUN Li-jie;SHI Yu-guang;ZHANG Xiao-yu;SHU Meng-ni;CHEN Mo-yang;YU Jian-wu;Department of Infectious Diseases,The Second Affiliated Hospital,Harbin Medical University;
出处 《肝脏》 2017年第7期602-604,659共4页 Chinese Hepatology
基金 国家自然科学基金资助项目(81370541,81501794)
关键词 丙型肝炎病毒 核心蛋白 沉默信息调节因子1 SIRT1 肝星状细胞 脂联素受体 Hepatitis C virus Core protein Silent information regulator 1 Hepatic stellate cells Adiponectin receptor
作者简介 通信作者:于建武,Email:yujianwu45@sina.com.cn
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  • 1Ruggieri A,Murdolo M,Harada T,et al.Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing hepatitis C virus core protein.Arch Virol,2004,149:61-74. 被引量:1
  • 2Hahn CS,Cho YG,Kang BS,et al.The HCV core protein acts as a positive regulator of Fas mediated apoptosis in a human lymphoblastoid T cell line.Virology,2000,276:127-137. 被引量:1
  • 3Tai DI,Tsai SL,Chen YM,et al.Activation of nuclear factor kappaB in hepatitis C virus infection implications for pathogenesis and hepatocarcinogenesis.Hepatology,2000,31:656-664. 被引量:1

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