ISSN 1001-5256
CN 22-1108/R
Volume 35 Issue 12
Dec.  2019
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Article Contents

Biological characteristics of high-mobility group box-1 and its role in the development,progression,and treatment of hepatitis B virus-related liver diseases

DOI: 10.3969/j.issn.1001-5256.2019.12.031
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  • Received Date: 2019-07-15
  • Published Date: 2019-12-20
  • High-mobility group box-1( HMGB1) is a member of the high-mobility group proteins and is present in eukaryotic cells.HMGB1 is not only a nuclear protein but also a pro-inflammatory factor,and the increase in HMGB1 level in the body indicates cell destruction and inflammatory response. Hepatitis B virus( HBV) infection is a major cause of chronic hepatitis B,liver cirrhosis,and hepatocellular carcinoma in the world. In recent years,the role of HMGB1 in HBV-related liver diseases has attracted more and more attention,especially the important role of HMGB1 in the progression of liver inflammation and liver cancer. This article reviews the recent research advances in the role of HMGB1 in the development,progression,and treatment of HBV-related liver diseases.


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  • [1] KRAUSE A,HABERKORN U,MIER W. Strategies for the treatment of HBV/HDV[J]. Eur J Pharmacol,2018,833:379-391.
    [2] TACKE F. Current and future therapy of hepatitis B and D[J].Dtsch Med Wochenschr,2019,144(8):528-534.
    [3] CAI J,HAN T,NIE C,et al. Biomarkers of oxidation stress,inflammation,necrosis and apoptosis are associated with hepatitis B-related acute-on-chronic liver failure[J]. Clin Res Hepatol Gastroenterol,2016,40(1):41-50.
    [4] FERRARI S,FINELLI P,ROCCHI M,et al. The active gene that encodes human high mobility group 1 protein(HMG1)contains introns and maps to chromosome 13[J]. Genomics,1996,35(2):367-371.
    [5] JIA L,CLEAR A,LIU FT,et al. Extracellular HMGB1 promotes differentiation of nurse-like cells in chronic lymphocytic leukemia[J]. Blood,2014,123(11):1709-1719.
    [6] ANDERSSON U,TRACEY KJ. HMGB1 is a therapeutic target for sterile inflammation and infection[J]. Annu Rev Immunol,2011,29:139-162.
    [7] WEIR HM,KRAULIS PJ,HILL CS,et al. Structure of the HMG box motif in the B-domain of HMG1[J]. EMBO J,1993,12(4):1311-1319.
    [8] JIANG Y,STEINLE JJ. HMGB1 inhibits insulin signalling through TLR4 and RAGE in human retinal endothelial cells[J]. Growth Factors,2018,36(3-4):164-171.
    [9] LOTZE MT,TRACEY KJ. High-mobility group box 1 protein(HMGB1):Nuclear weapon in the immune arsenal[J]. Nat Rev Immunol,2005,5(4):331-342.
    [10] LI J,KOKKOLA R,TABIBZADEH S,et al. Structural basis for the proinflammatory cytokine activity of high mobility group box1[J]. Mol Med,2003,9(1-2):37-45.
    [11] CATO L,STOTT K,WATSON M,et al. The interaction of HMGB1 and linker histones occurs through their acidic and basic tails[J]. J Mol Biol,2008,384(5):1262-1272.
    [12] CALOGERO S,GRASSI F,AGUZZI A,et al. The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice[J]. Nat Genet,1999,22(3):276-280.
    [13] CIUCCI A,GABRIELE I,PERCARIO ZA. HMGB1 and cord blood:Its role as immuno-adjuvant factor in innate immunity[J]. PLo S One,2011,6(8):e23766.
    [14] HREGGVIDSDOTTIR HS,OSTBERG T,WAHAMAA H,et al.The alarmin HMGB1 acts in synergy with endogenous and exogenous danger signals to promote inflammation[J]. J Leukoc Biol,2009,86(3):655-662.
    [15] CHEN RC,YI PP,ZHOU RR,et al. The role of HMGB1-RAGE axis in migration and invasion of hepatocellular carcinoma cell lines[J]. Mol Cel Biochem,2014,390(1-2):271-280.
    [16] ZHANG CL,SHU MG,QI HW,et al. Inhibition of tumor angiogenesis by HMGB1 A box peptide[J]. Med Hypotheses,2008,70(2):343-345.
    [17] KANG R,CHEN R,ZHANG Q,et al. HMGB1 in health and disease[J]. Mol Aspects Med,2014,40:1-116.
    [18] ANDERSSON U,HARRIS HE. The role of HMGB1 in the pathogenesis of rheumatic disease[J]. Biochim Biophys Acta,2010,1799(1-2):141-148.
    [19] LEE H,SHIN N,SONG M,et al. Analysis of nuclear high mobility group box 1(HMGB1)-binding proteins in colon cancer cells:Clustering with proteins involved in secretion and extranuclear function[J]. J Proteome Res,2010,9(9):4661-4670.
    [20] KAZAMA H,RICCI JE,HERNDON JM,et al. Induction of immunological tolerance by apoptotic cells requires caspasedependent oxidation of high-mobility group box-1 protein[J]. Immunity,2008,29(1):21-32.
    [21] HUDSON BI,CARTER AM,HARJA E,et al. Identification,classification,and expression of RAGE gene splice variants[J]. FASEB J,2008,22(5):1572-1580.
    [22] DEMLING N,EHRHARDT C,KASPER M,et al. Promotion of cell adherence and spreading:A novel function of RAGE,the highly selective differentiation marker of human alveolar epithelial type I cells[J]. Cell Tissue Res,2006,323(3):475-488.
    [23] HE SJ,CHENG J,FENG X,et al. The dual role and therapeutic potential of high-mobility group box 1 in cancer[J]. Oncotarget,2017,8(38):64534-64550.
    [24] XU Y,ZHOU Y,LIN H,et al. Toll-like receptor 2 in promoting angiogenesis after acute ischemic injury[J]. Int J Mol Med,2013,31(3):555-560.
    [25] YANG X,JIANG X,CHEN G,et al. T cell Ig mucin-3 promotes homeostasis of sepsis by negatively regulating the TLR response[J]. J Immunol,2013,190(5):2068-2079.
    [26] WONG D,KORZ W. Translating an antagonist of chemokine receptor CXCR4:From bench to bedside[J]. Clin Cancer Res,2008,14(24):7975-7980.
    [27] SCHIRALDI M,RAUCCI A,MUNOZ LM,et al. HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4[J].J Exp Med,2012,209(3):551-563.
    [28] MF AKBAR S,AL MAHTAB M,S IK. Nature of host immunity during hepatitis B virus infection and designing immune therapy[J]. Euroasian J Hepatogastroenterol,2018,8(1):42-46.
    [29] FU S,WANG J,HU X,et al. Crosstalk between hepatitis B virus X and high-mobility group box 1 facilitates autophagy in hepatocytes[J]. Mol Oncol,2018,12(3):322-338.
    [30] LI J,ZENG C,ZHENG B,et al. HMGB1-induced autophagy facilitates hepatic stellate cells activation:A new pathway in liver fibrosis[J]. Clin Sci(Lond),2018,132(15):1645-1667.
    [31] WANG LW,CHEN H,GONG ZJ. High mobility group box-1protein inhibits regulatory T cell immune activity in liver failure in patients with chronic hepatitis B[J]. Hepatobiliary Pancreat Dis Int,2010,9(5):499-507.
    [32] LI G,JIANG Q,XU K. CREB family:A significant role in liver fibrosis[J]. Biochimie,2019,163:94-100.
    [33] KAO YH,JAWAN B,GOTO S,et al. High-mobility group box 1 protein activates hepatic stellate cells in vitro[J]. Transplant Proc,2008,40(8):2704-2705.
    [34] KAO YH,JAWAN B,GOTO S,et al. Inhibition of high-mobility group box 1 expression by siRNA in rat hepatic stellate cells[J]. World J Gastroenterol,2011,17(36):4090-4098.
    [35] HE Q,FU Y,DING X,et al. High-mobility group box 1 induces endoplasmic reticulum stress and activates hepatic stellate cells[J]. Lab Invest,2018,98(9):1200-1210.
    [36] BI MR,ZHU LY,YAN BZ,et al. Association of upregulated HMGB1 and c-IAP2 proteins with hepatocellular carcinoma development and progression[J]. Hepat Mon,2014,14(12):e23552.
    [37] YAN W,CHANG Y,LIANG X,et al. High-mobility group box1 activates caspase-1 and promotes hepatocellular carcinoma invasiveness and metastases[J]. Hepatology,2012,55(6):1863-1875.
    [38] CHEN M,LIU Y,VARLEY P,et al. High-mobility group box1 promotes hepatocellular carcinoma progression through mir-21-mediated matrix metalloproteinase activity[J]. Cancer Res,2015,75(8):1645-1656.
    [39] YAN HX,WU HP,ZHANG HL,et al. P53 promotes inflammation-associated hepatocarcinogenesis by inducing HMGB1release[J]. J Hepatol,2013,59(4):762-768.
    [40] SITIA G,IANNACONE M,MULLER S,et al. Treatment with HMGB1 inhibitors diminishes CTL-induced liver disease in HBV transgenic mice[J]. J Leukoc Biol,2007,81(1):100-107.
    [41] YANG XY,KANG FB,YE LH,et al. Level of high-mobility group box 1 in patients with chronic hepatitis B and liver cirrhosis and its clinical significance[J]. J Clin Hepatol,2018,34(9):1901-1904.(in Chinese)杨新英,康富标,叶立红,等.慢性乙型肝炎及肝硬化患者血清高迁移率族蛋白B1水平变化及临床意义[J].临床肝胆病杂志,2018,34(9):1901-1904.
    [42] TU CT,YAO QY,XU BL,et al. Protective effects of curcumin against hepatic fibrosis induced by carbon tetrachloride:Modulation of high-mobility group box 1,Toll-like receptor 4 and2 expression[J]. Food Chem Toxicol,2012,50(9):3343-3351.
    [43] VENEREAU E,CASALGRANDI M,SCHIRALDI M,et al. Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release[J]. J Exp Med,2012,209(9):1519-1528.
    [44] YANG H,HREGGVIDSDOTTIR HS,PALMBLAD K,et al. A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release[J].Proc Natl Acad Sci U S A,2010,107(26):11942-11947.
    [45] ABEYAMA K,STERN DM,ITO Y,et al. The N-terminal domain of thrombomodulin sequesters high-mobility group-B1protein,a novel antiinflammatory mechanism[J]. J Clin Invest,2005,115(5):1267-1274.
    [46] XIE K,YU Y,PEI Y,et al. Protective effects of hydrogen gas on murine polymicrobial sepsis via reducing oxidative stress and HMGB1 release[J]. Shock,2010,34(1):90-97.
    [47] WANG L,ZHANG X,LIU L,et al. Atorvastatin protects rat brains against permanent focal ischemia and downregulates HMGB1,HMGB1 receptors(RAGE and TLR4),NF-kappaB expression[J]. Neurosci Lett,2010,471(3):152-156.
    [48] YANG M,CAO L,XIE M,et al. Chloroquine inhibits HMGB1inflammatory signaling and protects mice from lethal sepsis[J]. Biochem Pharmacol,2013,86(3):410-418.
    [49] ULLOA L,OCHANI M,YANG H,et al. Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation[J]. Proc Natl Acad Sci U S A,2002,99(19):12351-12356.
    [50] WANG H,LI W,LI J,et al. The aqueous extract of a popular herbal nutrient supplement,Angelica sinensis,protects mice against lethal endotoxemia and sepsis[J]. J Nutr,2006,136(2):360-365.
    [51] LI W,LI J,ASHOK M,et al. A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator,high mobility group box 1[J]. J Immunol,2007,178(6):3856-3864.
    [52] LI W,ASHOK M,LI J,et al. A major ingredient of green tea rescues mice from lethal sepsis partly by inhibiting HMGB1[J]. PLo S One,2007,2(11):e1153.
    [53] CHENG LS,LI J,LIU Y,et al. HMGB1-induced autophagy:A new pathway to maintain Treg function during chronic hepatitis B virus infection[J]. Clin Sci(Lond),2017,131(5):381-394.
    [54] TANG D,KANG R,ZEH HJ,et al. High-mobility group box1 and cancer[J]. Biochim Biophys Acta,2010,1799(1-2):131-140.
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