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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 36 Issue 5
May  2020
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Article Contents

Cell signaling pathways associated with liver fibrosis and potential therapeutic strategies

DOI: 10.3969/j.issn.1001-5256.2020.05.043
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  • Published Date: 2020-05-20
  • Liver fibrosis is a chronic liver injury caused by various etiologies and a complex pathological change with the activation of hepatic stellate cells as the central link, and various signaling pathways are involved in the regulation of such complex lesions. It has the dual nature of repair and damage and may eventually progress to liver cirrhosis, liver failure, and even liver cancer. In recent years, rapid progress has been made in the basic research on the cell signal transduction pathways associated with liver fibrosis, and some achievements have been made in the research on the treatment strategy of liver fibrosis. This article briefly reviews the cell signaling pathways associated with the de-/STAT signaling pathway, the NF-κB signaling pathway, the MAPK signaling pathway, the Smad signaling pathway, the Wnt signaling pathway, the Hedgehog signaling pathway, and the Notch signaling pathway,and also introduces the potential therapeutic strategies for liver fibrosis at present.

     

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  • [1] KOYAMA Y, BRENNER DA. Liver inflammation and fibrosis[J]. J Clin Invest, 2017, 127(1):55-64.
    [2] ZHANGDI HJ, SU SB, WANG F, et al. Crosstalk network among multiple inflammatory mediators in liver fibrosis[J].World J Gastroenterol, 2019, 25(33):4835-4849.
    [3] PAN J, JU J. Current perspectives on the JAK/STAT signaling pathway and its activating factors in liver fibrosis[J]. J Clin Hepatol, 2013, 29(5):393-396.(in Chinese)潘金,琚坚.JAK/STAT信号转导通路在肝纤维化形成中的作用[J].临床肝胆病杂志,2013, 29(5):393-396.
    [4] WANG WZ, MENG MH, KONG L, et al. Role of Jak/Stat pathway in CCl4-induced rat liver fibrosis model and molecular action mechanism of Fuzheng Huayu recipe in treatment of liver fibrosis[J]. J Clin Hepatol, 2014, 30(4):344-348.(in Chinese)王卫真,孟明辉,孔丽,等.Jak/Stat信号通路在经典CCl4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响[J].临床肝胆病杂志,2014, 30(4):344-348.
    [5] YAN DL, SHAO WB, GE C, et al. Effect of ligustrazine on JAK2/STAT3 signaling pathway in hepatic fibrosis induced by canavin A in mice[J]. Chin Hepatol, 2018, 23(3):255-259.(in Chinese)严栋梁,邵伟斌,葛创,等.川芎嗪对刀豆蛋白A诱导的小鼠肝纤维化JAK2/STAT3信号通路的影响[J].肝脏,2018, 23(3):255-259.
    [6] LI WW, WANG QC, SONG XW, et al. Correlation of the expression of NF-κB p65 and hepatic fibrosis in hepatitis patients[J]. Natl Med J China, 2012, 92(27):1886-1888.(in Chinese)李伟伟,王全楚,宋新文,等.核转录因子κB p65与肝炎肝纤维化的相关性分析[J].中华医学杂志,2012, 92(27):1886-1888.
    [7] ZHAO ZH, XU JM, MEI Q, et al. A contimuous observation of role of NF-κB in rats liver fibrosis[J]. Chin J Clin Healthc,2010, 13(5):496-498.(in Chinese)赵宗豪,许建明,梅俏,等.动态观察核转录因子kappaB在肝纤维化形成中的作用[J].中国临床保健杂志,2010, 13(5):496-498.
    [8] WU WJ, YANG MF, XU XB, et al. Expression and its location of p38MAPK in CCl4-induced hepatic fibrosis in rats[J].World Chin J Dig, 2008, 16(34):3822-3827.(in Chinese)吴文娟,杨妙芳,许小兵,等.p38 MAPK在大鼠实验性肝纤维化发生中的表达及其意义[J].世界华人消化杂志,2008, 16(34):3822-3827.
    [9] LI ZT, LI J, HUANG C, et al. Dynamic expression of MAPK signaling pathway on recovery hepatic fibrosis rats induced by CCl4[J]. Chin Pharmacol Bull, 2011, 27(6):809-814.(in Chinese)李政通,李俊,黄成,等.CCl4诱导的大鼠肝纤维化模型肝纤维化逆转与MAPK信号通路的研究[J].中国药理学通报,2011,27(6):809-814.
    [10] XU F, LIU C, ZHOU D, et al. TGF-β/SMAD pathway and its regulation in hepatic fibrosis[J]. J Histochem Cytochem,2016, 64(3):157-167.
    [11] XU JY, SHUAI ZL, XIE Y, et al. Expressions of TGF-β1,BMP-7 and Gremlin in CCl4-induced liver fibrosis tissue of mice[J]. Chin J Mod Med, 2017, 27(26):13-17.(in Chinese)徐靖宇,帅张丽,谢远,等.TGF-β1、BMP-7及Gremlin在小鼠肝纤维化组织中的表达[J].中国现代医学杂志,2017, 27(26):13-17.
    [12] XU AJ, XUE JY, YU SY, et al. The correlation of serum TGF-β1 content with liver fibrosis and Th1/Th2 immune levels in patients with chronic hepatitis B[J]. J Hainan Med Univ, 2018,24(2):195-197, 201.(in Chinese)徐爱静,薛建亚,余思雨,等.慢性乙肝患者血清TGF-β1含量检测及与肝纤维化、Th1/Th2免疫水平的相关关系[J].海南医学院学报,2018, 24(2):195-197, 201.
    [13] ZHAO DK, LUO WW, YU SP. Role of the Wnt signaling pathway in the development and progression of liver fibrosis[J]. J Clin Hepatol, 2018, 34(11):2415-2419.(in Chinese)赵东康,骆伟伟,余水平.Wnt信号通路与肝纤维化发生发展的关系[J].临床肝胆病杂志,2018, 34(11):2415-2419.
    [14] NISHIKAWA K, OSAWA Y, KIMURA K. Wnt/β-catenin signaling as a potential target for the treatment of liver cirrhosis using antifibrotic drugs[J]. Int J Mol Sci, 2018, 19(10):e3103.
    [15] GE WS, WANG YJ, WU JX, et al.β-catenin is overexpressed in hepatic fibrosis and blockage of Wnt/β-catenin signaling inhibits hepatic stellate cell activation[J]. Mol Med Rep, 2014, 9(6):2145-2151.
    [16] KONG JH, SIEBOLD C, ROHATGI R. Biochemical mechanisms of vertebrate hedgehog signaling[J]. Development,2019, 146(10):dev166892.
    [17] HU L, LIN X, LU H, et al. An overview of hedgehog signaling in fibrosis[J]. Mol Pharmacol, 2015, 87(2):174-182.
    [18] GAO L, ZHANG Z, ZHANG P, et al. Role of canonical Hedgehog signaling pathway in liver[J]. Int J Biol Sci, 2018,14(12):1636-1644.
    [19] VERDELHO MACHADO M, DIEHL AM. The hedgehog pathway in nonalcoholic fatty liver disease[J]. Crit Rev Biochem Mol Biol, 2018, 53(3):264-278.
    [20] FENG J, WANG C, LIU T, et al. Procyanidin B2 inhibits the activation of hepatic stellate cells and angiogenesis via the Hedgehog pathway during liver fibrosis[J]. J Cell Mol Med,2019, 23(9):6479-6493.
    [21] ZHANG X, LIU P, MU YP. Relationship between the Notch signaling pathway and the development and progression of liver fibrosis[J]. J Clin Hepatol, 2018, 34(1):181-183.(in Chinese)张旭,刘平,慕永平.Notch信号通路与肝纤维化发生发展的关系[J].临床肝胆病杂志,2018, 34(1):181-183.
    [22] MU YP, ZHANG X, XU Y, et al. Notch signaling pathway participates in the differentiation of hepatic progenitor cells into bile duct epithelial cells and progression of hepatic fibrosis in cholestatic liver fibrosis rat[J]. Chin J Pathol, 2017, 46(6):400-405.(in Chinese)慕永平,张笑,徐莹,等.Notch信号通路参与大鼠胆汁性肝纤维化肝祖细胞向胆管上皮细胞分化以及肝纤维化进展[J].中华病理学杂志,2017, 46(6):400-405.
    [23] CHEN Y, ZHENG S, QI D, et al. Inhibition of Notch signaling by aγ-secretase inhibitor attenuates hepatic fibrosis in rats[J]. PLoS One, 2012, 7(10):e46512.
    [24] TRAUTWEIN C, FRIEDMAN SL, SCHUPPAN D, et al. Hepatic fibrosis:Concept to treatment[J]. J Hepatol, 2015, 62(1Suppl):s15-s24.
    [25] Chinese Society of Hepatology, Chinese Medical Association;Chinese Society of Gastroenterology, Chinese Medical Association; Chinese Society of Infectious Diseases, Chinese Medical Association. Consensus on the diagnosis and therapy of hepatic fibrosis(2019)[J]. J Clin Hepatol, 2019, 35(10):2163-2172.(in Chinese)中华医学会肝病学分会,中华医学会消化病学分会,中华医学会感染病学分会.肝纤维化诊断及治疗共识(2019年)[J].临床肝胆病杂志,2019, 35(10):2163-2172.
    [26] NI Q, DING K, WANG KQ, et al. Deletion of HNF1αin hepatocytes results in fatty liver-related hepatocellular carcinoma in mice[J]. FEBS Lett, 2017, 591(13):1947-1957.
    [27] YAO LJ, DENG X, DING CH, et al. Overexpression of hepatocyte nuclear factor 1αmediated by adeno-associated virus attenuates carbon tetrachloride-induced hepatic fibrosis in mice[J]. Acad J Second Military Med Univ, 2017, 38(9):1098-1105.(in Chinese)姚荔嘉,邓星,丁晨虹,等.腺相关病毒介导的肝细胞核因子1α过表达改善四氯化碳诱导的小鼠肝纤维化[J].第二军医大学学报,2017, 38(9):1098-1105.
    [28] QIAN H, DENG X, HUANG ZW, et al. An HNF1α-regulated feedback circuit modulates hepatic fibrogenesis via the crosstalk between hepatocytes and hepatic stellate cells[J].Cell Res, 2015, 25(8):930-945.
    [29] GE SF, CHENG N, YU YQ, et al. Changes in the expression of high-mobility group box 1 and hepatocyte nuclear factor1αduring the formation of liver fibrosis and their correlation with liver fibrosis score:An experimental study[J]. Chin J Hepatol, 2017, 25(5):386-388.(in Chinese)葛善飞,程娜,余燕青,等.肝纤维化形成中高迁移率族蛋白1与肝细胞核因子1α的表达变化及相关性的实验研究[J].中华肝脏病杂志,2017, 25(5):386-388.
    [30] ZHAO JW, WANG YG, SHI M. Role of extracellular vesicles in diagnosis and treatment of liver fibrosis[J]. World Chin J Dig,2019, 27(8):515-520.(in Chinese)赵佳伟,王玉刚,施敏.细胞外囊泡在肝纤维化诊治中的研究进展[J].世界华人消化杂志,2019, 27(8):515-520.
    [31] CHEN L, CHEN R, KEMPER S, et al. Therapeutic effects of serum extracellular vesicles in liver fibrosis[J]. J Extracell Vesicles, 2018, 7(1):1461505.
    [32] POVERO D, PINATEL EM, LESZCZYNSKA A, et al. Human induced pluripotent stem cell-derived extracellular vesicles reduce hepatic stellate cell activation and liver fibrosis[J]. JCI Insight, 2019, 4(14):e125652.
    [33] EOM YW, SHIM KY, BAIK SK. Mesenchymal stem cell therapy for liver fibrosis[J]. Korean J Intern Med, 2015, 30(5):580-589.
    [34] XU DS, WAN AN, CHEN Y, et al. Liver fibrosis and stem cell therapy[J]. J Shanghai Jiaotong Univ(Med Sci), 2017, 37(3):403-406.(in Chinese)徐栋生,万爱妮,陈蕴,等.肝纤维化与干细胞疗法[J].上海交通大学学报(医学版),2017, 37(3):403-406.
    [35] DU C, JIANG M, WEI X, et al. Transplantation of human matrix metalloproteinase-1 gene-modified bone marrow-derived mesenchymal stem cell attenuates CCl4-induced liver fibrosis in rats[J]. Int J Mol Med, 2018, 41(6):3175-3184.
    [36] MEHRABANI D, KHAJEHAHMADI Z, TAJIK P, et al. Regenerative effect of bone marrow-derived mesenchymal stem cells in thioacetamide-induced liver fibrosis of rats[J]. Arch Razi Inst, 2019, 74(3):279-286.
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