中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R

留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

PNPLA3 I148M基因突变对大鼠肝星状细胞转化生长因子β1表达的影响

安佰全 辛永宁 芦琳琳 宣世英

引用本文:
Citation:

PNPLA3 I148M基因突变对大鼠肝星状细胞转化生长因子β1表达的影响

DOI: 10.3969/j.issn.1001-5256.2016.04.035
基金项目: 

国家自然科学基金资助项目(81170337/H0304); 青岛市民生科技计划项目(14-2-3-17-nsh); 

详细信息
  • 中图分类号: R575.2

Effect of PNPLA3 I148M mutation on expression of TGF- β1 in rat hepatic stellate cells

Research funding: 

 

  • 摘要:

    目的探讨patatin样磷脂酶域(PNPLA3)I148M基因突变在非酒精性脂肪性肝纤维化发生发展中的作用机制。方法构建携带PNPLA3 I148M基因突变型和野生型的慢病毒载体,转染大鼠肝星状细胞(HSC-T6),采用实时荧光定量PCR的方法检测转化生长因子(TGF)β1 mRNA的表达水平。采用t检验进行组间比较。结果构建了携带PNPLA3 I148M突变型和野生型的慢性病毒载体,并成功转染HSC-T6细胞,建立了能够稳定表达PNPLA3突变型和野生型基因的HSC-T6细胞系;PNPLA3 I148M突变型与野生型相比,TGFβ1 mRNA相对表达量明显上调,差异具有统计学意义(1.25±0.15 vs 0.48±0.07,t=11.826,P<0.001)。结论PNPLA3 I148M基因突变能够促进HSC中TGFβ1的表达,为进一步探讨PNPLA3 I148M基因突变在非酒精性脂肪性肝纤维化中的作用提供了细胞模型和新的研究思路。

     

  • [1]RAY K.Liver:hepatic stellate cells hold the key to liver fibrosis[J].Nat Rev Gastroenterol Hepatol,2014,11(2):74.
    [2]INAGAKI Y,HIGASHIYAMA R,HIGASHI K.Novel anti-fibrotic modalities for liver fibrosis:molecular targeting and regenerative medicine in fibrosis therapy[J].J Gastroenterol Hepatol,2012,27(Suppl 2):85-88.
    [3]SPELIOTES EK,YERGES-ARMSTRONG LM,WU J,et al.Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits[J].PLoS Genet,2011,7(3):e1001324.
    [4]HE S,MCPHAUL C,LI JZ,et al.A sequence variation(I148M)in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis[J].J Biol Chem,2010,285(9):6706-6715.
    [5]PETTA S,MIELE L,BUGIANESI E,et al.Glucokinase regulatory protein gene polymorphism affects liver fibrosis in non-alcoholic fatty liver disease[J].PLoS One,2014,9(2):e87523.
    [6]KRAWCZYK M,GRUNHAGE F,LAMMERT F.Identification of combined genetic determinants of liver stiffness within the SREBP1c-PNPLA3 pathway[J].Int J Mol Sci,2013,14(10):21153-21166.
    [7]ZAIN SM,MOHAMED R,MAHADEVA S,et al.A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease[J].Hum Genet,2012,131(7):1145-1152.
    [8]TREPO E,PRADAT P,POTTHOFF A,et al.Impact of patatinlike phospholipase-3(rs738409 C>G)polymorphism on fibrosis progression and steatosis in chronic hepatitis C[J].Hepatology,2011,54(1):60-69.
    [9]KRAWCZYK M,GRUNHAGE F,ZIMMER V,et al.Variant adiponutrin(PNPLA3)represents a common fibrosis risk gene:noninvasive elastography-based study in chronic liver disease[J].JHepatol,2011,55(2):299-306.
    [10]KAJDANIUK D,MAREK B,BORGIEL-MAREK H,et al.Transforming growth factor beta1(TGFbeta1)in physiology and pathology[J].Endokrynol Pol,2013,64(5):384-396.
    [11]BAGHY K,IOZZO RV,KOVALSZKY I.Decorin-TGFbeta axis in hepatic fibrosis and cirrhosis[J].J Histochem Cytochem,2012,60(4):262-268.
    [12]CHIANG DJ,ROYCHOWDHURY S,BUSH K,et al.Adenosine2A receptor antagonist prevented and reversed liver fibrosis in a mouse model of ethanol-exacerbated liver fibrosis[J].PLoS One,2013,8(7):e69114.
    [13]OZAKI I,HAMAJIMA H,MATSUHASHI S,et al.Regulation of TGF-beta1-induced pro-apoptotic signaling by growth factor receptors and extracellular matrix receptor integrins in the liver[J].Front Physiol,2011,2:78.
  • 加载中
计量
  • 文章访问数:  2096
  • HTML全文浏览量:  47
  • PDF下载量:  401
  • 被引次数: 0
出版历程
  • 出版日期:  2016-04-20
  • 分享
  • 用微信扫码二维码

    分享至好友和朋友圈

目录

    /

    返回文章
    返回