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

肝纤维化相关信号转导通路研究进展

彭琴 赵绅君 李武

引用本文:
Citation:

肝纤维化相关信号转导通路研究进展

DOI: 10.3969/j.issn.1001-5256.2017.05.035
基金项目: 

云南省自然科学基金(2009CD087); 

详细信息
  • 中图分类号: R575.2

Research advances in signaling pathways involved in the development of hepatic fibrosis

Research funding: 

 

  • 摘要: 肝纤维化是肝脏对各种慢性肝损伤进行自我修复的一种病理过程,最终进展为肝硬化、肝衰竭,甚至肝癌。如何早期干预和治疗肝纤维化显得尤为重要。总结了TGFβ/Smad信号通路、Notch信号通路、Wnt信号通路、Hedgehog信号通路及整合素信号通路在肝纤维化发生机制中的最新研究进展,指出各信号通路在肝纤维化的发生发展中发挥极其重要的作用,有望为肝纤维化的治疗提供新的方向。

     

  • [1]YANG Y, KIM B, PARK YK, et al.Astaxanthin prevents TGFβ1-induced pro-fibrogenic gene expression by inhibiting Smad3 activation in hepatic stellate cells[J].Biochim Biophys Acta, 2015, 1850 (1) :187-185.
    [2]CAO Y, XIA YZ, CHEN J, et al.Anti-fibrosis effects of deoxyschizandrin in human hepatic stellate cells[J].Chin J Clin Pharmacol Ther, 2016, 21 (8) :878-883. (in Chinese) 曹媛, 夏延哲, 陈杰, 等.五味子甲素在人肝星状细胞中的抗纤维化作用[J].中国临床药理学与治疗学, 2016, 21 (8) :878-883.
    [3]BATALLER R, BRENNER DA.Liver fibrosis[J].J Clin Invest, 2005, 115 (2) :209-218.
    [4] LUO SZ, LI ZH, XU MY, et al.Reversal of liver fibrosis through AG490 inhibition of the TGFβ1-STAT3 pathway[J].Chin J Hepatol, 2015, 23 (12) :939-943. (in Chinese) 罗声政, 李郑红, 徐铭益, 等.AG490抑制转化生长因子β1-STAT3信号通路逆转肝纤维化的机制研究[J].中华肝脏病杂志, 2015, 23 (12) :939-943.
    [5]ZHOU XL, YU SP.Role of Wnt signaling pathway in progression of liver cirrhosis[J].J Clin Hepatol, 2015, 31 (9) :1540-1542. (in Chinese) 周雪玲, 余水平.Wnt信号通路对肝硬化进展的影响[J].临床肝胆病杂志, 2015, 31 (9) :1540-1542.
    [6]REN CZ, HAO LS.Signal transduction involved in activation of hepatic stellate cells[J].J Clin Hepatol, 2015, 31 (3) :452-456. (in Chinese) 任昌镇, 郝礼森.肝星状细胞活化过程中的信号转导[J].临床肝胆病杂志, 2015, 31 (3) :452-456.
    [7]FABREGAT I, MORENO-CACERES J, SANCHEZ A, et al.TGF-βsignalling and liver disease[J].FEBS J, 2016, 283 (12) :2219-2232.
    [8] MASSAGUE J.TGFβsignalling in context[J].Nat Rev Mol Cell Biol, 2012, 13 (10) :616-630.
    [9]HANYU A, ISHIDOU Y, EBISAWA T, et al.The N domain of Smad7 is essential for specific inhibition of transforming growth factor-beta signaling[J].J Cell Biol, 2001, 155 (6) :1017-1027.
    [10]DOOLEY S, HAMZAVI J, BREIKOPF K, et al.Smad7 prevents activation of hepatic stellate cells and liver fibrosis in rats[J].Gastroenterology, 2003, 125 (1) :178-191.
    [11]SCHULTZE-MOSGAU S, BLAESE MA, GRABENBAUER G, et al.Smad-3 and Smad-7 expression following anti-transforming growth factor beta 1 (TGFbeta1) -treatment in irradiated rat tissue[J].Radiother Oncol, 2004, 70 (3) :249-259.
    [12]BALTA C, HERMAN H, BOLDURA OM, et al.Chrysin attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway[J].Chem Biol Interact, 2015, 240:94-101.
    [13]ARGENTOU N, GERMANIDIS G, HYTIROGLOU P, et al.TGF-βsignaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment[J].Inflamm Res, 2016, 65 (5) :355-365.
    [14]GEISLER F, STRAZZABOSCO M.Emerging roles of Notch signaling in liver disease[J].Hepatology, 2015, 61 (1) :382-392.
    [15]CHEN Y, ZHENG S, Qi D, et al.Inhibition of Notch signaling by aγ-secretase inhibitor attenuates hepatic fibrosis in rats[J].PLo SOne, 2012, 7 (10) :e46512.
    [16]ZHANG X, DU G, XU Y, et al.Inhibition of notch signaling pathway prevents cholestatic liver fibrosis by decreasing the differentiation of hepatic progenitor cells into cholangiocytes[J].Lab Invest, 2016, 96 (3) :350-360.
    [17]TANRIVERDI G, KAYA-DAGISTANLI F, AYLA S, et al.Resveratrol can prevent CCl 4-induced liver injury by inhibiting Notch signaling pathway[J].Histol Histopathol, 2016, 31 (7) :769-784.
    [18]CHEN YX, WENG ZH, QI D, et al.Effect of Notch signaling on the activation of hepatic stellate cells[J].Chin J Hepatol, 2012, 20 (9) :677-682. (in Chinese) 陈毅雄, 翁志宏, 祁丹, 等.调控Notch信号对肝星状细胞活化的影响[J].中华肝脏病杂志, 2012, 20 (9) :677-682.
    [19]ZHANG QD, XU MY, CAI XB, et al.Myofibroblastic transformation of rat hepatic stellate cells:the role of Notch signaling and epithelial-mesenchymal transition regulation[J].Eur Rev Med Pharmacol Sci, 2015, 19 (21) :4130-4138.
    [20]BANSAL R, BAARLEN JV, STORM G, et al.The interplay of the Notch signaling in hepatic stellate cells and macrophages determines the fate of liver fibrogenesis[J].Sci Rep, 2015, 5:18272.
    [21]THOMPSON MD, MONGA SP.WNT/beta-catenin signaling in liver health and disease[J].Hepatology, 2007, 45 (5) :1298-1305.
    [22]CHENG JH, SHE H, HAN YP, et al.Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis[J].Am J Physiol Gastrointest Liver Physiol, 2008, 294 (1) :g39-g49.
    [23]LIN X, KONG LN, HUANG C, et al.Hesperetin derivative-7 inhibits PDGF-BB-induced hepatic stellate cell activation and proliferation by targeting Wnt/β-catenin pathway[J].Int Immunopharmacol, 2015, 25 (2) :311-320.
    [24]MONGA SP.Role of Wnt/β-catenin signaling in liver metabolism and cancer[J].Int J Biochem Cell Biol, 2011, 43 (7) :1021-1029.
    [25]ZHANG Y, ZHANG H, PENG R, et al.Mechanism research on Artesunate in the treatment of liver fibrosis by inhibiting miR-154/β-catenin in hepatic stellate cell[J].China Med Herald, 2016, 13 (1) :35-38. (in Chinese) 张英, 张洪, 彭锐, 等.青蒿琥酯抑制肝星状细胞microRNA-154/β-catenin治疗肝纤维化的机制研究[J].中国医药导报, 2016, 13 (1) :35-38.
    [26]MA ZG, LV XD, ZHAN LL, et al.Human urokinase-type plasminogen activator gene-modified bone marrow-derived mesenchymal stem cells attenuate liver fibrosis in rats by down-regulating the Wnt signaling pathway[J].World J Gastroenterol, 2016, 22 (6) :2092-2103.
    [27]MICHELOTTI GA, XIE G, SWIDERSKA M, et al.Smoothened is a master regulator of adult liver repair[J].J Clin Invest, 2013, 123 (6) :2380-2394.
    [28]VELCHETI V, GOVINDAN R.Hedgehog signaling pathway and lung cancer[J].J Thorac Oncol, 2007, 2 (1) :7-10.
    [29]PEREIRA TA, XIE G, CHOI SS, et al.Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni[J].Liver Int, 2013, 33 (1) :149-161.
    [30]XIE G, KARACA G, SWIDERSKA-SYN M, et al.Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice[J].Hepatology, 2013, 58 (5) :1801-1813.
    [31]CHE L, YUAN YH, JIA J, et al.Activation of sonic hedgehog signaling pathway is an independent potential prognosis predictor in human hepatocellular carcinoma patients[J].Chin J Cancer Res, 2012, 24 (4) :323-331.
    [32]HOOPER JE, SCOTT MP.Communicating with Hedgehogs[J].Na Rev Mol Cell Biol, 2005, 6 (4) :306-317.
    [33]LI T, LENG XS, ZHU JY, et al.Suppression of hedgehog signaling regulates hepatic stellate cell activation and collagen secretion[J].Int J Clin Exp Pathol, 2015, 8 (11) :14574-14579.
    [34]USCHNER FE, RANABHAT G, CHOI SS, et al.Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension[J].Sci Rep, 2015, 5:14573.
    [35]YANG JJ, TAO H, LI J.Hedgehog signaling pathway as key player in liver fibrosis:new insights and perspectives[J].Expert Opin T-her Targets, 2014, 18 (9) :1011-1021.
    [36]YU F, LU Z, CHEN B, et al.Salvianolic acid B-induced microR-NA-152 inhibits liver fibrosis by attenuating DNMT1‐mediated Patched1 methylation[J].J Cell Mol Med, 2015, 19 (11) :2617-2632.
    [37]EIAGROUDY NN, EINAGA RN, EIRAZEQ RA, et al.Forskolin, a hedgehog signaling inhibitor, attenuates carbon tetrachloride-induced liver fibrosis in rats[J].Br J Pharmacol, 2016, 173 (22) :3248-3260.
    [38]ZHANG K, JIANG MN, ZHANG CH, et al.Effect of Gan-fukang compound on hepatic expression of integrinα5β1/FAK signal pathway in carbon tetrachloride-induced liver fibrosis in rats[J].J Clin Hepatol, 2012, 15 (2) :104-107. (in Chinese) 张坤, 姜妙娜, 张彩华, 等.肝复康对肝纤维化大鼠肝组织整合素α5β1/FAK信号通路的调节作用[J].实用肝脏病杂志, 2012, 15 (2) :104-107.
    [39]ELAHARKAWY AM, OAKLEY F, MANN DA.The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis[J].Apoptosis, 2005, 10 (5) :927-939.
    [40]BI H, MING L, CHENG R, et al.Liver extracellular matrix promotes BM-MSCs hepatic differentiation and reversal of liver fibrosis through activation of integrin pathway[J].J Tissue Eng Regen Med, 2016.[Epub ahead of print]
    [41]SUGIYAMA A, KANNO K, NISHIMICHI N, et al.Periostin promotes hepatic fibrosis in mice by modulating hepatic stellate cell activation viaαv integrin interaction[J].J Gastroenterol, 2016, 51 (12) :1161-1174.
  • 加载中
计量
  • 文章访问数:  2855
  • HTML全文浏览量:  34
  • PDF下载量:  550
  • 被引次数: 0
出版历程
  • 收稿日期:  2016-11-14
  • 出版日期:  2017-05-20
  • 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