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人胰岛素样生长因子-1的体外抗肝纤维化活性

万爱妮, 徐栋生, 蔡燕飞, 陈蕴, 金坚, 李华钟

万爱妮, 徐栋生, 蔡燕飞, 陈蕴, 金坚, 李华钟. 人胰岛素样生长因子-1的体外抗肝纤维化活性[J]. 中国药科大学学报, 2017, 48(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20170413
引用本文: 万爱妮, 徐栋生, 蔡燕飞, 陈蕴, 金坚, 李华钟. 人胰岛素样生长因子-1的体外抗肝纤维化活性[J]. 中国药科大学学报, 2017, 48(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20170413
WAN Aini, XU Dongsheng, CAI Yanfei, CHEN Yun, JIN Jian, LI Huazhong. Anti-liver fibrosis activities of human insulin-like growth factor-1 in vitro[J]. Journal of China Pharmaceutical University, 2017, 48(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20170413
Citation: WAN Aini, XU Dongsheng, CAI Yanfei, CHEN Yun, JIN Jian, LI Huazhong. Anti-liver fibrosis activities of human insulin-like growth factor-1 in vitro[J]. Journal of China Pharmaceutical University, 2017, 48(4): 476-482. DOI: 10.11665/j.issn.1000-5048.20170413

人胰岛素样生长因子-1的体外抗肝纤维化活性

基金项目: 国家高技术研究发展计划(863计划)资助项目(No.2014AA021003);江苏省优势学科建设工程资助项目(PADA)

Anti-liver fibrosis activities of human insulin-like growth factor-1 in vitro

  • 摘要: 探讨人胰岛素样生长因子-1(IGF-1)的体外抗肝纤维化作用。检测IGF-1对人正常肝细胞L-02增殖及生长周期的影响;建立CCl4诱导的肝细胞损伤模型,探究IGF-1抗肝细胞损伤活性;以TGF-β1诱导的肝星状细胞HSC-T6为体外肝纤维化研究模型,检测IGF-1对HSC-T6细胞中纤维化相关蛋白表达水平及对胞内TGF-β1/Smad信号通路的影响。结果显示,IGF-1可解除TGF-β1对L-02生长的抑制作用,提高CCl4损伤L-02的细胞存活率,降低HSC-T6细胞纤维化相关蛋白表达水平,抑制TGF-β1/Smad信号通路中Smad3的磷酸化。结果表明,IGF-1能够促进肝细胞增殖,保护肝细胞免受损伤,干预TGF-β1/Smad信号通路,抑制胞外基质ECM合成,从而发挥抗肝纤维化效果。
    Abstract: This study was focus on investigating the anti-liver fibrosis effects of insulin-like growth factor-1(IGF-1) in vitro. The effects of IGF-1 on human liver L-02 cell viability and cell cycle were observed. CCl4-induced L-02 cell injury was set up to detect the anti-apoptotic activity of insulin-like growth factor-1(IGF-1). Transforming growth factor β1(TGF-β1)induced hepatic stellate cell line(HSC-T6)were used as a liver fibrosis model in vitro to analyze the effects of IGF-1 on the expression of liver fibrosis proteins and intracellular TGF-β1/Smad signaling pathway in HSC-T6 cells. The results showed that IGF-1 could relieve the growth inhibition effects of TGF-β1 on L-02 cells, increase the viability of L-02 cells injured by CCl4, decrease the expression of liver fibrosis proteins, and inhibit the TGF-β1/Smad signaling pathway by inhibiting the phosphorylation of Smad3. Our study suggested that IGF-1 exerted anti-liver fibrosis effects by stimulating L-02 cells proliferation, reducing cell damage and inhibiting ECM accumulation via interfering TGF-β1/Smad signaling pathway.
  • [1] Hernandez-Gea V, Friedman SL. Pathogenesis of liver fibrosis[J].Annu Rev Pathol,2011,6(1):425-456.
    [2] Bataller R,Brenner DA.Liver fibrosis[J].J Clin Invest,2005,115(2):209-218.
    [3] Friedman SL.Molecular regulation of hepatic fibrosis,an integrated cellular response to tissue injury[J].J Biol Chem,2000,275(4):2247-2250.
    [4] Brandao DF,Ramalho LN,Ramalho FS,et al.Liver cirrhosis and hepatic stellate cells[J].Acta Cir Bras,2006,21(Suppl 1):54-57.
    [5] Lee UE,Friedman SL.Mechanisms of hepatic fibrogenesis[J].Best Pract Res:Clin Gastroenyerol,2011,25(2):195-206.
    [6] Wells RG. Cellular sources of extracellular matrix in hepatic fibrosis[J].Clin Liver Dis,2008,12(4):759-768.
    [7] Gressner AM,Weiskirchen R.Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-beta as major players and therapeutic targets[J].J Cell Mol Med,2006,10(1):76-99.
    [8] Gressner AM,Weiskirchen R,Breitkopf K,et al.Roles of TGF-beta in hepatic fibrosis[J].Front Biosci,2002,7(1/2/3):d793-d807.
    [9] Foo NP, Lin SH, Lee YH, et al. Alpha-lipoic acid inhibits liver fibrosis through the attenuation of ROS-triggered signaling in hepatic stellate cells activated by PDGF and TGF-beta[J].Toxicol,2011,282(1/2):39-46.
    [10] Laron Z.Insulin-like growth factor 1(IGF-1):a growth hormone[J].Mol Pathol,2001,54(5):311-316.
    [11] Karen B,Søren M.Insulin-like growth factor-I and the liver[J].Liver Int,2011,31(7):911-919.
    [12] Blomsma MC,deKnegt RJ,Dullaart RP,et al.Insulin-like growth factor-1 in liver cirrhosis[J].J Hepatol,1997,27(6):1133-1138.
    [13] CastillaCortazar I,Garcia M,Muguerza B,et al.Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis[J].Gastroenterol,1997,113(5):1682-1691.
    [14] Muguerza B,Castilla-Cortazar I,Garcia M,et al.Antifibrogenic effect in vivo of low doses of insulin-like growth factor-I in cirrhotic rats[J].Acta Biochim Biophys,2001,1536(2/3):185-195.
    [15] Chen XX,Xie J,Chen H,et al.EZH2 plays a role in HSC-T6 cell proliferation and activation affecting MAPK/ERK and PI3 K/AKT pathway[J].Chin Pharm Bull(中国药理学通报),2015,31(8):1061-1065.
    [16] Xu T,Ni MM,Li X,et al.NLRC5 regulates TGF-β1-induced proliferation and activation of hepatic stellate cells during hepatic fibrosis[J].Inter J Biochem Cell B,2016,70:92-104.
    [17] Friedman SL.Liver fibrosis-from bench to bedside[J].J Hepatol,2003,38(Suppl 1):S38-S53.
    [18] Reeves HL,Friedman SL.Activation of hepatic stellate cells-a key issue in liver fibrosis[J].Front Biosci,2002,7(1-3):d808-d826.
    [19] Watanabe T,Niioka M,Hozawa S,et al.Gene expression of interstitial collagenase in both progressive and recovery phase of rat liver fibrosis induced by carbon tetrachloride[J].J Hepatol,2000,33(2):224-235.
    [20] Wang L,Potter JJ,Rennie-Tankersley L,et al.Effects of retinoic acid on the development of liver fibrosis produced by carbon tetrachloride in mice[J].Biochim Biophys Acta,2007,1772(1):66-71.
    [21] Yin G,Ping L,Xu P.Hepatoprotective and antioxidant effects of Glycyrrhiza glabra extract against carbon tetrachloride(CCl(4))-induced hepatocyte damage in common carp(Cyprinus carpio)[J].Fish Physiol Biochem,2011,37(1):209-216.
    [22] Liu SQ, Yu JP, Ran ZX. Experimental study on Ginkgo Biloba extract against carbon tetrachloride-induced chronic liver damage in rats[J].J China Pharm Univ(中国药科大学学报),2003,34(1):61-64.
    [23] Zhong LF,Zhang JG,Zhang FQ,et al.Mechanisms of carbon tetrachloride-induced liver injury in rats[J].Chin J Pharm Toxicol(中国药理学与毒理学),1989,3(4):298-303.
    [24] Recknagel RO,Glende EA,Dolak JA,et al.Mechanisms of carbon tetrachloride toxicity[J].Pharmacol Ther,1989,43(1):139-154.
    [25] Basu S.Carbon tetrachloride-induced lipid peroxidation:eicosanoid formation and their regulation by antioxidant nutrients[J].Toxicol,2003,189(1/2):113-127.
    [26] CastillaCortazar I,Garcia M,Muguerza B,et al.Hepatoprotective effects of insulin-like growth factor I in rats with carbon tetrachloride-induced cirrhosis[J].Gastroentelogy,1997,113(5):1682-1691.
    [27] Nakamura I,Zakharia K,Banini BA,et al.Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF,VEGF and PDGF signaling[J].PLoS ONE,2014,9(4):e92273.
    [28] Sprenger H,Kaufmann A,Garn H,et al.Induction of neutrophil-attracting chemokines in transforming rat hepatic stellate cells[J].Gastroenterol,1997,113(1):277-285.
    [29] Kitamura Y,Ninomiya H.Smad expression of hepatic stellate cells in liver cirrhosis in vivo and hepatic stellate cell line in vitro[J].Pathol Int,2003,53(1):18-26.
    [30] Zheng Y,Zhao C,Wang F,et al.Effects and mechanisms of stilbene glucoside on the proliferation and collagen synthesis of cardiac fibroblasts stimulated by TGF-β1[J].J China Pharm Univ(中国药科大学学报),2014,45(3):362-367.
    [31] Uemura M,Swenson ES,Gaça MD,et al.Smad2 and Smad3 play different roles in rat hepatic stellate cell function and Smooth muscle actin organization[J].Mol Cell Biol,2005,16(9):4214-4224.
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出版历程
  • 刊出日期:  2017-08-24

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