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

多种细胞在肝纤维化逆转中的作用

王林 刘学恩 庄辉

引用本文:
Citation:

多种细胞在肝纤维化逆转中的作用

DOI: 10.3969/j.issn.1001-5256.2018.04.036
基金项目: 

国家"十三五"艾滋病和病毒性肝炎等重大传染病防治科技重大专项(2017ZX10302401-003-015); 

详细信息
  • 中图分类号: R575.2

Cellular mechanisms in liver fibrosis regression

Research funding: 

 

  • 摘要:

    在多种慢性肝损伤病因的作用下,肝星状细胞(HSC)等活化为肌成纤维细胞(MFB),迁移至损伤部位并大量分泌细胞外基质(ECM),ECM在肝内过度沉积,从而形成肝纤维化。当肝损伤病因被移除或经过有效治疗后,肝纤维化可发生逆转。介绍了多种细胞参与肝纤维化的逆转过程,MFB通过自身衰老、凋亡、失活,在肝纤维化逆转中发挥关键作用;巨噬细胞通过加快ECM降解和诱导MFB衰老等发挥抗肝纤维化功能;肝窦内皮细胞通过维持其正常表型阻断并逆转肝纤维化;自然杀伤细胞杀伤处于活化早期的HSC和衰老的MFB,参与肝纤维化逆转。

     

  • [1]ZOUBEK ME, TRAUTWEIN C, STRNAD P.Reversal of liver fibrosis:from fiction to reality[J].Best Pract Res Clin Gastroenterol, 2017, 31 (2) :129-141.
    [2]ELPEK GO.Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:an update[J].World J Gastroenterol, 2014, 20 (23) :7260-7276.
    [3]SCHUPPAN D.Liver fibrosis:common mechanisms and antifibrotic therapies[J].Clin Res Hepatol Gastroenterol, 2015, 39 (Suppl1) :s51-s59.
    [4]TACKE F, TRAUTWEIN C.Mechanisms of liver fibrosis resolution[J].J Hepatol, 2015, 63 (4) :1038-1039.
    [5]SNOWDON VK, FALLOWFIELD JA.Models and mechanisms of fibrosis resolution[J].Alcohol Clin Exp Res, 2011, 35 (5) :794-799.
    [6]ELLIS EL, MANN DA.Clinical evidence for the regression of liver fibrosis[J].J Hepatol, 2012, 56 (5) :1171-1180.
    [7]HINZ B.Myofibroblasts[J].Exp Eye Res, 2016, 142 (1) :56-70.
    [8]SCHAFER S, VISWANATHAN S, WIDJAJA AA, et al.IL11 is a crucial determinant of cardiovascular fibrosis[J].Nature, 2017, 552 (7683) :110-115.
    [9]ARAVINTHAN AD, ALEXANDER GJ.Senescence in chronic liver disease:is the future in aging?[J].J Hepatol, 2016, 65 (4) :825-834.
    [10]COLLADO M, BLASCO MA, SERRANO M.Cellular senescence in cancer and aging[J].Cell, 2007, 130 (2) :223-233.
    [11]KRIZHANOVSKY V, YON M, DICKINS RA, et al.Senescence of activated stellate cells limits liver fibrosis[J].Cell, 2008, 134 (4) :657-667.
    [12]JUN JI, LAU LF.The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing[J].Nat Cell Biol, 2010, 12 (7) :676-685.
    [13]KONG X, FENG D, WANG H, et al.Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis[J].Hepatology, 2012, 56 (3) :1150-1159.
    [14]CHEN J, PAN J, WANG J, et al.Soluble egg antigens of Schistosoma japonicum induce senescence in activated hepatic stellate cells by activation of the STAT3/p53/p21 pathway[J].Sci Rep, 2016, 6 (7) :e2315.
    [15]JIN H, LIAN N, ZHANG F, et al.Activation of PPARγ/P53 signaling is required for curcumin to induce hepatic stellate cell senescence[J].Cell Death Dis, 2016, 7 (4) :e2189.
    [16]KLEIN S, KLOSEL J, SCHIERWAGEN R, et al.Atorvastatin inhibits proliferation and apoptosis, but induces senescence in hepatic myofibroblasts and thereby attenuates hepatic fibrosis in rats[J].Lab Invest, 2012, 92 (10) :1440-1450.
    [17]JIN H, LIAN N, FENG Z, et al.Inhibition of YAP signaling contributes to senescence of hepatic stellate cells induced by tetramethylpyrazine[J].Eur J Pharm Sci, 2017, 96:323-333.
    [18]NISHIZAWA H, IGUCHI G, FUKUOKA H, et al.IGF-I induces senescence of hepatic stellate cells and limits fibrosis in a p53-dependent manner[J].Sci Rep, 2016, 6:34605.
    [19]ELMORE S.Apoptosis:a review of programmed cell death[J].Toxicol Pathol, 2007, 35 (4) :495-516.
    [20]YANG W, DU J, NIU X, et al.MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2[J].Cell Death Dis, 2017, 8 (5) :e2792.
    [21]BORKHAM-KAMPHORST E, SCHAFFRATH C, van de LEUR E, et al.The anti-fibrotic effects of CCN1/CYR61 in primary portal myofibroblasts are mediated through induction of reactive oxygen species resulting in cellular senescence, apoptosis and attenuated TGF-βsignaling[J].Biochim Biophys Acta, 2014, 1843 (5) :902-914.
    [22]WANG J, CHU ES, CHEN HY, et al.microRNA-29b prevents liver fibrosis by attenuating hepatic stellate cell activation and inducing apoptosis through targeting PI3K/AKT pathway[J].Oncotarget, 2015, 6 (9) :7325-7338.
    [23]CHEN Q, CHEN L, WU X, et al.Dihydroartemisinin prevents liver fibrosis in bile duct ligated rats by inducing hepatic stellate cell apoptosis through modulating the PI3K/Akt pathway[J].IUBMB Life, 2016, 68 (3) :220-231.
    [24]PARK SM, JUNG EH, KIM JK, et al.20S-Protopanaxadiol, an aglycosylated ginsenoside metabolite, induces hepatic stellate cell apoptosis through liver kinase B1-AMP-activated protein kinase activation[J].J Ginseng Res, 2017, 41 (3) :392-402.
    [25]KIM WH, MATSUMOTO K, BESSHO K, et al.Growth inhibition and apoptosis in liver myofibroblasts promoted by hepatocyte growth factor leads to resolution from liver cirrhosis[J].Am J Pathol, 2005, 166 (4) :1017-1028.
    [26]MADANKUMAR P, NAVEENKUMAR P, DEVARAJ H, et al.Morin, a dietary flavonoid, exhibits anti-fibrotic effect and induces apoptosis of activated hepatic stellate cells by suppressing canonical NF-κB signaling[J].Biochimie, 2015, 110:107-118.
    [27]TROEGER JS, MEDERACKE I, GWAK GY, et al.Deactivation of hepatic stellate cells during liver fibrosis resolution in mice[J].Gastroenterology, 2012, 143 (4) :1073-1083.
    [28]KISSELEVA T, CONG M, PAIK Y, et al.Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis[J].Proc Natl Acad Sci U S A, 2012, 109 (24) :9448-9453.
    [29]JIN H, TERAI S, SAKAIDA I.The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis[J].J Gastroenterol, 2007, 42 (6) :475-484.
    [30]GODICHAUD S, KRISA S, COURONNE B, et al.Deactivation of cultured human liver myofibroblasts by trans-resveratrol, a grapevine-derived polyphenol[J].Hepatology, 2000, 31 (4) :922-931.
    [31]VILASECA M, GARCI A-CALDERO H, LAFOZ E, et al.The anticoagulant rivaroxaban lowers portal hypertension in cirrhotic rats mainly by deactivating hepatic stellate cells[J].Hepatology, 2017, 65 (6) :2031-2044.
    [32]IREDALE JP, BATALLER R.Identifying molecular factors that contribute to resolution of liver fibrosis[J].Gastroenterology, 2014, 146 (5) :1160-1164.
    [33]RAMACHANDRAN P, PELLICORO A, VERNON MA, et al.Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis[J].Proc Natl Acad Sci U S A, 2012, 109 (46) :e3186-e3195.
    [34]JIANG Z, JIANG JX, ZHANG GX.Macrophages:a double-edged sword in experimental autoimmune encephalomyelitis[J].Immunol Lett, 2014, 160 (1) :17-22.
    [35]BAECK C, WEI X, BARTNECK M, et al.Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C+macrophage infiltration in mice[J].Hepatology, 2014, 59 (3) :1060-1072.
    [36]FOMIN ME, ZHOU Y, BEYER AI, et al.Production of factor VIII by human liver sinusoidal endothelial cells transplanted in immunodeficient u PA mice[J].PLo S One, 2013, 8 (10) :e77255.
    [37]DELEVE LD, WANG X, GUO Y.Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence[J].Hepatology, 2008, 48 (3) :920-930.
    [38]DELEVE LD.Liver sinusoidal endothelial cells in hepatic fibrosis[J].Hepatology, 2015, 61 (5) :1740-1746.
    [39]XIE G, WANG X, WANG L, et al.Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats[J].Gastroenterology, 2012, 142 (4) :918-927.
    [40]HYDES T, ABUHILAL M, ARMSTRONG T, et al.Natural killer cell maturation markers in the human liver and expansion of an NKG2C+KIR+population[J].Lancet, 2015, 385:s45.
    [41]MELHEM A, MUHANNA N, BISHARA A, et al.Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC[J].J Hepatol, 2006, 45 (1) :60-71.
    [42]YI HS, LEE YS, BYUN JS, et al.Alcohol dehydrogenase III exacerbates liver fibrosis by enhancing stellate cell activation and suppressing natural killer cells in mice[J].Hepatology, 2014, 60 (3) :1044-1053.
    [43]JIN H, JIA Y, YAO Z, et al.Hepatic stellate cell interferes with NK cell regulation of fibrogenesis via curcumin induced senescence of hepatic stellate cell[J].Cell Signal, 2017, 33:79-85.
  • 加载中
计量
  • 文章访问数:  2118
  • HTML全文浏览量:  48
  • PDF下载量:  437
  • 被引次数: 0
出版历程
  • 出版日期:  2018-04-20
  • 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