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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 9
Sep.  2016
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Article Contents

Current research status of mechanisms of the development and progression of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2016.09.039
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  • Published Date: 2016-09-20
  • Liver fibrosis is the intermediate process in the progression of various chronic liver diseases to liver cirrhosis,and its serious complications affect the prognosis of patients with chronic liver diseases. However,so far,there remain no effective drugs for the treatment of liver fibrosis. This article investigates the development and progression of liver fibrosis from the aspects of signaling pathways and molecular mechanisms and briefly introduces the latest research advances in the roles of signaling pathways,including transforming growth factor- β/Smad pathway,platelet- derived growth factor pathway,leptin signaling pathway,and connective tissue growth factor pathway,chemokines,neuroendocrine factors,and angiogenesis in the development of liver fibrosis,so as to enhance the knowledge of the development of liver fibrosis and provide a theoretical basis for the research on molecular- targeted drugs based on the pathogenesis of liver fibrosis.

     

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  • [1]LEE YA,WALLACE MC,FRIEDMAN SL.Pathobiology of liver fibrosis:a translational success story[J].Gut,2015,64(5):830-841.
    [2]PUCHE JE,SAIMAN Y,FRIEDMAN SL.Hepatic stellate cells and liver fibrosis[J].Compr Physiol,2013,3(4):1473-1492.
    [3]GOTO K,LIN W,ZHANG L,et al.The AMPK-related kinase SNARK regulates hepatitis C virus replication and pathogenesis through enhancement of TGF-βsignaling[J].J Hepatol,2013,59(5):942-948.
    [4]LI T,YAN Y,WANG B,et al.Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis[J].Stem Cells Dev,2013,22(6):845-854.
    [5]WANG SY,YUAN MZ,LIU XD,et al.Advance research on relationship between cytokines and pulmonary fibrosis[J].J Jilin Univ:Med Edit,2014,40(6):1325-1329.(in Chinese)王司仪,原铭贞,刘笑玎,等.细胞因子与肺纤维化相关性的研究进展[J].吉林大学学报:医学版,2014,40(6):1325-1329.
    [6]YANG L,PANG Y,MOSES HL.TGF-beta and immune cells:an important regulatory axis in the tumor microenvironment and progression[J].Trends Immunol,2010,31(6):220-227.
    [7]WU FR,PAN CX,RONG C,et al.Inhibition of acid-sensing ion channel 1a in hepatic stellate cells attenuates PDGF-induced activation of HSCs through MAPK pathway[J].Mol Cell Biochem,2014,395(1):199-209.
    [8]OGAWA S,OCHI T,SHIMADA H,et al.Anti-PDGF-B monoclonal antibody reduces liver fibrosis development[J].Hepatol Res,2010,40(11):1128-1141.
    [9]HONG F,CHOU H,FIEL MI,et al.Antifibrotic activity of sorafenib in experimental hepatic fibrosis:refinement of inhibitory targets,dosing,and window of efficacy in vivo[J].Dig Dis Sci,2013,58(1):257-264.
    [10]ABDEL-MONEIM AM,AL-KAHTANI MA,EL-KERSH MA,et al.Free radical-scavenging,anti-inflammatory/anti-fibrotic and hepatoprotective actions of taurine and silymarin against CCl4induced rat liver damage[J].PLo S One,2015,10(12):e0144509.
    [11]HANDY JA,FU PP,KUMAR P,et al.Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis[J].Biochem J,2011,440(3):385-395.
    [12]ZHOU Q,GUAN W,QIAO H,et al.GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation[J].Biochim Biophys Acta,2014,1842(12):2367-2377.
    [13]WANG MJ,MA H.Role of adiponectin in liver fibrogenesis:progress in basic and clinical research[J].J Clin Hepatol,2011,27(3):321-324.(in Chinese)王美娟,马红.脂联素在肝纤维化发生中的作用[J].临床肝胆病杂志,2011,27(3):321-324.
    [14]DONG Z,SU L,ESMAILI S,et al.Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells[J].J Mol Med(Berl),2015,93(12):1327-1339.
    [15]CHEN L,CHARRIER AL,LEASK A,et al.Ethanol-stimulated differentiated functions of human or mouse hepatic stellate cells are mediated by connective tissue growth factor[J].J Hepatol,2011,55(2):399-406.
    [16]GRESSNER OA,LAHME B,DEMIRCI I,et al.Differential effects of TGF-βon connective tissue growth factor(CTGF/CCN2)expression in hepatic stellate cells and hepatocytes[J].J Hepatol,2007,47(5):699-710.
    [17]FERDOUSHI S,PAUL D,GHOSH CK.Correlation of connective tissue growth factor(CTGF/CCN2)with hepatic fibrosis in chronic hepatitis B[J].Mymensingh Med J,2015,24(3):558-563.
    [18]WANG Q,USINGER W,NICHOLS B,et al.Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease[J].Fibrogenesis Tissue Repair,2011,4(1):1-11.
    [19]MARRA F,TACKE F.Roles for chemokines in liver disease[J].Gastroenterology,2014,147(3):577-594.
    [20]LIANG YJ,LUO J,LU Q,et al.Gene profile of chemokines on hepatic stellate cells of schistosome-infected mice and antifibrotic roles of CXCL9/10 on liver non-parenchymal cells[J].PLo S One,2012,7(8):e42490.
    [21]BARASHI N,WEISS ID,WALD O,et al.Inflammation-induced hepatocellular carcinoma is dependent on CCR5 in mice[J].Hepatology,2013,58(3):1021-1030.
    [22]SAHIN H,BORKHAM-KAMPHORST E,KUPPE C,et al.Chemokine CXCL9 attenuates liver fibrosis-associated angiogenesis in mice[J].Hepatology,2012,55(5):1610-1619.
    [23]LIU LY,ALEXA K,CORTES M,et al.Cannabinoid receptor signaling regulates liver development and metabolism[J].Development,2016,143(4):609-622.
    [24]GUILLOT A,HAMDAOUI N,BIZY A,et al.Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver[J].Hepatology,2014,59(1):296-306.
    [25]YANG YY,TSAI TH,HUANG YT,et al.Hepatic endothelin-1 and endocannabinoids-dependent effects of hyperleptinemia in nonalcoholic steatohepatitis-cirrhotic rats[J].Hepatology,2012,55(5):1540-1550.
    [26]HUANG HC,WANG SS,HSIN IF,et al.Cannabinoid receptor 2agonist ameliorates mesenteric angiogenesis and portosystemic collaterals in cirrhotic rats[J].Hepatology,2012,56(1):248-258.
    [27]de MINICIS S,CANDELARESI C,MARZIONI M,et al.Role of endogenous opioids in modulating HSC activity in vitro and liver fibrosis in vivo[J].Gut,2008,57(3):352-364.
    [28]KIM DC,JUN DW,KWON YI,et al.5-HT2A receptor antagonists inhibit hepatic stellate cell activation and facilitate apoptosis[J].Liver Int,2013,33(4):535-543.
    [29]ZVIBEL I,ATIAS D,PHILLIPS A,et al.Thyroid hormones induce activation of rat hepatic stellate cells through increased expression of p75 neurotrophin receptor and direct activation of Rho[J].Lab Invest,2010,90(5):674-684.
    [30]FERNANDEZ M.Molecular pathophysiology of portal hypertension[J].Hepatology,2015,61(4):1406-1415.
    [31]FALLOWFIELD JA,HAYDEN AL,SNOWDON VK,et al.Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo[J].Hepatology,2014,59(4):1492-1504.
    [32]DUONG HT,DONG Z,SU L,et al.The use of nanoparticles to deliver nitric oxide to hepatic stellate cells for treating liver fibrosis and portal hypertension[J].Small,2015,11(19):2291-2304.
    [33]ZHAN L,HUANG C,MENG XM,et al.Hypoxia-inducible factor-1alpha in hepatic fibrosis:a promising therapeutic target[J].Biochimie,2015,108(1):1-7.
    [34]SCHNABL B,BRENNER DA.Interactions between the intestinal microbiome and liver disease[J].Gastroenterology,2014,146(6):1513-1524.
    [35]CHEN Y,CHOI SS,MICHELOTTI GA,et al.Hedgehog controls hepatic stellate cell fate by regulating metabolism[J].Gastroenterology,2012,143(5):1319-1329.
    [36]MANN DA.Epigenetics in liver disease[J].Hepatology,2014,60(4):1418-1425.
    [37]OLSEN AL,BLOOMER SA,CHAN EP,et al.Hepatic stellate cells require a stiff environment for myofibroblastic differentiation[J].Am J Physiol Gastrointest Liver Physiol,2011,301(1):g110-g118.
    [38]MUNOZ-ESPIN D,SERRANO M.Cellular senescence:from physiology to pathology[J].Nat Rev Mol Cell Biol,2014,15(7):482-496.
    [39]ZENG YL,ZHANG XJ,SHANG J,et al.Single-chain human anti-EGFR antibody/truncated protamine fusion protein carrying Hsp47 siRNA can induce apoptosis of human hepatic stellate cells[J].Chin J Hepatol,2014,22(11):843-848.(in Chinese)曾艳丽,张晓菊,尚佳,等.携带Hsp47特异性siRNA的人源单链抗体融合蛋白诱导人原代肝星状细胞凋亡研究[J].中华肝脏病杂志,2014,22(11):843-848.
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