中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 3
Mar.  2017
Turn off MathJax
Article Contents

Pathogenesis and new therapeutic targets of liver fibrosis

DOI: 10.3969/j.issn.1001-5256.2017.03.001
  • Received Date: 2017-01-04
  • Published Date: 2017-03-20
  • In recent years, the basic research on liver fibrosis has been progressed rapidly.This article briefly reviews the cellular and molecular mechanisms of liver fibrosis, including the origin of myofibroblasts, immune regulation, autophagy, and epigenetic regulation, and introduces several new therapeutic targets.More and more evidences show that successful removal of causes is the most important antifibrotic therapy.At present, although the antifibrotic drugs acting on different targets have been emerging, most of them are still in the early stage of research and development, and well-designed clinical trials are needed to confirm their clinical efficacy.

     

  • loading
  • [1]XU J, KISSELEVA T.Bone marrow-derived fibrocytes contribute to liver fibrosis[J].Exp Biol Med (Maywood) , 2015, 240 (6) :691-700.
    [2]ELPEK GO.Cellular and molecular mechanisms in the pathogenesis of liver fibrosis:an update[J].World J Gastroentero, 2014, 20 (23) :7260-7276.
    [3]SEKI E, BRENNER DA.Recent advancement of molecular mechanisms of liver fibrosis[J].J Hepato-Bil-Pan Sci, 2015, 22 (7) :512-518.
    [4]DUFFIELD JS, FORBES SJ, CONSTANDINOU CM, et al.Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair[J].J Clin Invest, 2005, 115 (1) :56-65.
    [5]LI H, YOU H, FAN X, et al.Hepatic macrophages in liver fibrosis:pathogenesis and potential therapeutic targets[J].BMJ Open Gastroenterology, 2016, 3 (1) :e000079.
    [6] LEE YA, WALLACE MC, FRIEDMAN SL.Pathobiology of liver fibrosis:a translational success story[J].Gut, 2015, 64 (5) :830-841.
    [7]MARX V.Autophagy:eat thyself, sustain thyself[J].Nat Methods, 2015, 12 (12) :1121-1125.
    [8]MALLAT A, LODDER J, TEIXEIRA-CLERC F, et al.Autophagy:a multifaceted partner in liver fibrosis[J].Biomed Res Int, 2014, 2014 (8) :1-7.
    [9]ROY S, BENZ F, LUEDDE T, et al.The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis[J].Hepatobiliary Surg Nutr, 2015, 4 (1) :24-33.
    [10]RODERBURG C, MOLLNOW T, BONGAERTS B, et al.MicroRNA profiling in human serum reveals compartment-specific roles of miR-571 and miR-652 in liver cirrhosis[J].PLoS One, 2012, 7 (3) :e32999.
    [11]SZABO G, BALA S.MicroRNAs in liver disease[J].Nat Rev Gastro Hepat, 2013, 10 (9) :542-552.
    [12]ANADOL E, SCHIERWAGEN R, ELFIMOVA N, et al.Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients[J].Hepatology, 2015, 61 (1) :46-55.
    [13]XU S, WANG Y, TAI DC, et al.q Fibrosis:a fully-quantitative innovative method incorporating histological features to facilitate accurate fibrosis scoring in animal model and chronic hepatitis B patients[J].J Hepatol, 2014, 61 (2) :260-269.
    [14]SUN Y, ZHOU J, WANG L, et al.New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment[J].Hepatology, 2016.[Epub ahead of print]
    [15]BARANOVA A, LAL P, BIRERDINC A, et al.Non-invasive markers for hepatic fibrosis[J].BMC Gastroenterol, 2011, 11 (1) :91.
    [16]JIA J, HOU J, DING H, et al.Transient elastography compared to serum markers to predict liver fibrosis in a cohort of Chinese patients with chronic hepatitis B[J].J Gastroen Hepatol, 2015, 30 (4) :756-762.
    [17]CHENG J, HOU J, DING H, et al.Validation of ten noninvasive diagnostic models for prediction of liver fibrosis in patients with chronic hepatitis B[J].PLoS One, 2015, 10 (12) :e144425.
    [18]ELLIS EL, MANN DA.Clinical evidence for the regression of liver fibrosis[J].J Hepatol, 2012, 56 (5) :1171-1180.
    [19]D'AMBROSIO R, AGHEMO A, RUMI MG, et al.A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis[J].Hepatology, 2012, 56 (2) :532-543.
    [20]MARCELLIN P, GANE E, BUTI M, et al.Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B:a 5-year open-label follow-up study[J].Lancet, 2013, 381 (9865) :468-475.
    [21]NEVENS F, ANDREONE P, MAZZELLA G, et al.A Placebocontrolled trial of obeticholic acid in primary biliary cholangitis[J].N Engl J Med, 2016, 375 (7) :631-643.
    [22]NEUSCHWANDER-TETRI BA, LOOMBA R, SANYAL AJ, et al.Farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, non-alcoholic steatohepatitis (FLINT) :a multicentre, randomised, placebo-controlled trial[J].The Lancet, 2015, 385 (9972) :956-965.
    [23]FAGONE P, MANGANO K, PESCE A, et al.Emerging therapeutic targets for the treatment of hepatic fibrosis[J].Drug Discov Today, 2016, 21 (2) :369-375.
    [24]PALUMBO-ZERR K, ZERR P, DISTLER A, et al.Orphan nuclear receptor NR4A1 regulates transforming growth factor-βsignaling and fibrosis[J].Nat Med, 2015, 21 (2) :150-158.
    [25]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) :4.
    [26]CHAKRABORTY JB, MANN DA.NF-κB signalling:embracing complexity to achieve translation[J].J Hepatol, 2010, 52 (2) :285-291.
    [27]WU L, MAO C, MING X.Modulation of Bcl-x alternative splicing induces apoptosis of human hepatic stellate cells[J].Biomed Res Int, 2016, 2016 (2) :1-7.
    [28]GAO B, RADAEVA S, PARK O.Liver natural killer and natural killer T cells:immunobiology and emerging roles in liver diseases[J].J Leukoc Biol, 2009, 86 (3) :513-528.
    [29]CONG M, LIU T, WANG P, et al.Antifibrotic effects of a recombinant adeno-associated virus carrying small interfering RNA targeting TIMP-1 in rat liver fibrosis[J].Am J Pathol, 2013, 182 (5) :1607-1616.
    [30]BARRY-HAMILTON V, SPANGLER R, MARSHALL D, et al.Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment[J].Nat Med, 2010, 16 (9) :1009-1017.
    [31]MEISSNER EG, MCLAUGHLIN M, MATTHEWS L, et al.Simtuzumab treatment of advanced liver fibrosis in HIV and HCV-infected adults:results of a 6-month open-label safety trial[J].Liver Int, 2016, 36 (12) :1783-1792.
    [32]EOM YW, SHIM KY, BAIK SK.Mesenchymal stem cell therapy for liver fibrosis[J].Korean J Intern Med, 2015, 30 (5) :580-589.
    [33]SHI M, ZHANG Z, XU R, et al.Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients[J].Stem Cells Transl Med, 2012, 1 (10) :725-731.
    [34]WANG P, CONG M, LIU TH, et al.Primary isolated hepatic oval cells maintain progenitor cell phenotypes after two-year prolonged cultivation[J].J Hepatol, 2010, 53 (5) :863-871.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (2370) PDF downloads(619) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return