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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 4
Apr.  2018
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Article Contents

Cellular mechanisms in liver fibrosis regression

DOI: 10.3969/j.issn.1001-5256.2018.04.036
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  • Published Date: 2018-04-20
  • With the action of various chronic factors for liver injury, hepatic stellate cells (HSCs) are activated and transformed to myofibroblasts (MFBs) and then migrate to the injured part and secrete a large amount of extracellular matrix (ECM) .Excessive deposition of ECM in the liver causes liver fibrosis.The elimination of factors for liver injury or effective treatment helps to achieve liver fibrosis regression.This article introduces the types of cells involved in liver fibrosis regression.MFBs play an important role liver fibrosis regression via senescence, apoptosis, and inactivation; macrophages exert an anti-fibrosis effect by accelerating ECM degradation and inducing MFB senescence; liver sinusoidal endothelial cells help to achieve liver fibrosis regression by maintaining its normal phenotype; natural killer cells are involved in liver fibrosis regression by killing the early activated HSCs and senescent MFBs.

     

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  • [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.
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