Advertisement
Research Article| Volume 16, ISSUE 2, P325-339, June 1996

Hepatic Regeneration: The Role of Regeneration in Pathogenesis of Chronic Liver Diseases

DOI:https://doi.org/10.1016/S0272-2712(18)30272-5
Hepatic Regeneration: The Role of Regeneration in Pathogenesis of Chronic Liver Diseases
Previous ArticleHepatocellular Injury in Hepatitis B and C Virus Infections
Next ArticleLiver Regeneration in Health and Disease
      This paper is only available as a PDF. To read, Please Download here.
      Understanding of the cellular and molecular mechanisms involved in liver regeneration in response to various injuries has increased dramatically in recent years. The application of molecular biologic techniques has revealed an amazingly complex and sophisticated network of interacting cells, cytokines, and extracellular matrix molecules, which all communicate with each other with the goal of minimizing and repairing tissue damage. This article summarizes recent information on the role of cytokines and extracellular matrix in hepatic regeneration associated with virus and alcohol-induced chronic liver diseases.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Register: Create an account
      Institutional Access: Sign in to ScienceDirect

      References

        • Akerman P.A.
        • Cote P.M.
        • Yang S.Q.
        • et al.
        Long-term ethanol consumption alters the hepatic response to the regenerative effect of tumor necrosis factor-a.
        Hepatology. 1993; 17: 1066
        • Andres J.L.
        • DeFalcis D.
        • Noda M.
        • et al.
        Binding of two growth factor families to separate domains of the proteoglycan betaglycan.
        J Biol Chem. 1992; 267: 5927
        • Anthony P.P.
        • Ishak K.G.
        • Nayak N.C.
        • et al.
        The morphology of cirrhosis.
        J Clin Pathol. 1978; 31: 395
        • Bachem M.G.
        • Riess U.
        • Gressner A.M.
        Liver fat storing cell proliferation stimulated by epidermal growth factor/transforming growth factor alpha and inhibited by transforming growth factor beta.
        Biochem Biophys Res Common. 1989; 162: 708
        • Bedossa P.
        • Peltier E.
        • Terris B.
        • et al.
        Transforming growth factor-beta 1 (TGFβl) and TGFβl receptors in normal, cirrhotic, and neoplastic livers.
        Hepatology. 1995; 21: 760
        • Bird G.L.A.
        • Sheron N.
        • Goka A.K.J.
        • et al.
        Increased plasma tumor necrosis factor in severe alcoholic hepatitis.
        Ann Intern Med. 1990; 112: 917
        • Bisgaard H.C.
        • Nagy P.
        • Santoni-Rugiu E.A.
        • et al.
        Proliferation, apoptosis, and induction of hepatic transcription factors are characteristics of the early response of biliary epithelial (oval) cells to chemical carcinogens.
        Hepatology. 1996; 23: 62
        • Boccaccio C.
        • Gaudino G.
        • Gambarotta F.
        • et al.
        Hepatocyte growth factor receptor expression is inducible and is part of the delayed-early response to HGF.
        J Biol Chem. 1994; 269: 12846
        • Border W.A.
        • Rouslahti E.
        Transforming growth factor-β in disease: The dark side of tissue repair.
        J Clin Invest. 1992; 90: 1
        • Bucher N.L.R.
        • Malt R.A.
        Regeneration of Liver and Kidney. Little, Brown & Co, Boston1971
        • Chang H.K.
        • Wang B.Y.
        • Yuh C.H.
        • et al.
        A liver-specific nuclear factor interacts with the promotor region of the large surface protein gene of human hepatitis B virus.
        Mol Cell Biol. 1989; 9: 5189
        • Chisari F.V.
        • Klopchin K.
        • Moriyama T.
        • et al.
        Molecular pathogenesis of hepatocellular carcinoma in hepatitis B virus transgenic mice.
        Cell. 1989; 59: 1145
        • Desmet V.J.
        • Gerber M.
        • Hoofnagle J.H.
        • et al.
        Classification of chronic hepatitis: Diagnosing, grading and staging.
        Hepatology. 1994; 19: 1513
        • De Maeyer E.
        • De Maeyer-Guignard J.
        Interferons.
        in: Thomson A The Cytokine Handbook. Academic Press, San Diego1994: 265
        • De Vos R.
        • Desmet V.J.
        Ultrastructural characteristics of novel epithelial cell types identified in human pathologic specimens with chronic ductular reaction.
        Am J Pathol. 1992; 140: 1441
        • Dinarello C.A.
        Interleukin-1 and its biologically related cytokines.
        Adv Immunol. 1989; 44: 153
        • DiPersio C.M.
        • Jackson D.A.
        • Zareth K.S.
        The extracellular matrix coordinately modulates liver transcription factors and hepatocyte morphology.
        Mol Cell Biol. 1991; 11: 4405
        • Dunsford H.A.
        • Sell S.
        • Chisari F.V.
        Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice.
        Cancer Res. 1990; 50: 3400
        • Evarts R.P.
        • Nagy P.
        • Marsden E.
        • et al.
        A precursor-product relationship exists between oval cells and hepatocytes in rat liver.
        Carcinogenesis. 1987; 8: 1737
        • Evarts R.P.
        • Nagy P.
        • Nakatsukasa H.
        • et al.
        In vivo differentiation of rat liver oval cells into hepatocytes.
        Cancer Res. 1989; 49: 1541
        • Evarts R.P.
        • Nakatsukasa H.
        • Marsden E.R.
        • et al.
        Expression of transforming growth factor-alpha in regenerating liver and during hepatic differentiation.
        Mol Carcinog. 1992; 5: 25
        • Evarts R.P.
        • Hu Z.
        • Fujio K.
        • et al.
        Activation of hepatic stem cell compartment in the rat: Role of transforming growth factor a, hepatocyte growth factor, and acidic fibroblast growth factor in early proliferation.
        Cell Growth Differ. 1993; 4: 555
        • Fausto N.
        • Webber E.M.
        Control of liver growth.
        Crit Rev Eukaryotic Gene Expression. 1993; 3: 117
        • Feingold K.R.
        • Barker M.E.
        • Jones A.L.
        • et al.
        Localization of tumor necrosis factor-stimulated DNA synthesis in the liver.
        Hepatology. 1991; 13: 773
        • Freeswick P.D.
        • Geller D.
        • Lancaster J.R.
        • et al.
        Nitric oxide and the liver.
        in: Arias IM Boyer JL Fausto N The Liver: Biology and Pathobiology. ed 3. Raven Press, New York1994: 1031
        • French S.W.
        • Nash J.
        • Shitabata P.
        • et al.
        Pathology of alcoholic liver diseases.
        Semin Liv Dis. 1993; 13: 154
        • Frizell E.
        • Liu S-L
        • Abraham A.
        • et al.
        Expression of SPARC in normal and fibrotic livers.
        Hepatology. 1995; 21: 847
        • Fujio K.
        • Evarts R.P.
        • Hu Z.
        • et al.
        Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in the adult rat.
        Lab Invest. 1994; 70: 511
        • Geller D.A.
        • Nussler A.K.
        • Di Silvio M.
        • et al.
        Cytokines, endotoxin, and glucocorticoids regulate expression of inducible nitric oxide synthase in hepatocytes.
        Proc Natl Acad Sci U S A. 1993; 90: 522
        • Gerber M.A.
        • Thung S.N.
        • Shen S.
        • et al.
        Phenotypic characterization of hepatic proliferation, antigenic expression by proliferating epithelial cells in fetal liver, massive hepatic necrosis, and nodular transformation of the liver.
        Am J Pathol. 1983; 110: 70
        • Gressner A.M.
        Hepatic fibrogenesis: The puzzle of interacting cells, fibrogenic cytokines, regulatory loops, and extracellular matrix molecules.
        Z Gastroenterol. 1992; 30: 5
        • Hagen T.M.
        • Huang S.
        • Cumutte J.
        • et al.
        Extensive DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.
        Proc Natl Acad Sci U S A. 1994; 91: 12808
        • Hiramatsu N.
        • Hayashi N.
        • Katayama K.
        • et al.
        Immunohistochemical detection of fas antigen in liver tissue of patients with chronic hepatitis C.
        Hepatology. 1994; 19: 1354
        • Hsia C.C.
        • Evarts R.P.
        • Nakatsukasa H.
        • et al.
        Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.
        Hepatology. 1992; 16: 1327
        • Hsia C.C.
        • Thorgeirsson S.S.
        • Tabor E.
        Expression of hepatitis B surface and core antigens and transforming growth factor-a in “oval cells” of the liver of patients with hepatocellular carcinoma.
        J Med Virol. 1994; 43: 216
        • Hu Z.
        • Evarts R.P.
        • Fujio K.
        • et al.
        Expression of hepatocyte growth factor and c-met genes during hepatic differentiation and liver development.
        Am J Pathol. 1993; 142: 1823
        • Huggett A.C.
        • Ford C.P.
        • Thorgeirsson S.S.
        Effects of interleukin-6 on the growth of normal and transformed rat liver cells in culture.
        Growth Factors. 1989; 2: 83
        • Iredale J.P.
        • Arthur M.J.P.
        Hepatocyte-matrix interactions.
        Gut. 1994; 35: 729
        • Ishiki Y.
        • Ohnishi H.
        • Muto Y.
        • et al.
        Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo.
        Hepatology. 1992; 16: 1227
        • Itoh N.
        • Yonehara S.
        • Ishii A.
        • et al.
        The polypeptide encoded by cDNA for human cell surface antigen fas can mediate apoptosis.
        Cell. 1991; 66: 233
        • Jhappan C.
        • Stahle C.
        • Harkins R.N.
        • et al.
        TGFa over expression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas.
        Cell. 1990; 61: 1137
        • Johnson D.E.
        • Williams L.T.
        Structural and functional diversity in the FGF receptor multigene family.
        Adv Cancer Res. 1993; 60: 1
        • Kim C.M.
        • Koike K.
        • Saito I.
        • et al.
        The Hbx gene of hepatitis virus C induces liver cancer in transgenic mice.
        Nature. 1991; 351: 317
        • Lai Y.S.
        • Thung S.
        • Gerber M.A.
        • et al.
        Expression of cytokeratins in normal and diseased liver and in primary liver carcinomas.
        Arch Pathol Lab Med. 1989; 113: 134
        • Lee W.M.
        Acute liver failure.
        N Engl J Med. 1993; 329: 1362
        • Lemire J.M.
        • Shiojiri N.
        • Fausto N.
        Oval cell proliferation and the origin of small hepatocytes in liver injury induced by D-galactosamine.
        Am J Pathol. 1991; 139: 535
        • Liang T.J.
        • Jefferts L.J.
        • Reddy K.R.
        • et al.
        Viral pathogenesis of hepatocellular carcinoma in the United States.
        Hepatology. 1993; 18: 1326
        • Liu M.L.
        • Mars W.M.
        • Zamegar R.
        • et al.
        Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor alpha in adult rat liver.
        Hepatology. 1994; 19: 1521
        • Lopez-Casillas F.
        • Payne H.M.
        • Andres J.L.
        • et al.
        Betaglycan can act as a dual modulator of TGF-β access to signaling receptors: Mapping of ligand binding and GAG attachment sites.
        J Cell Biol. 1994; 124: 557
        • Lyon M.
        • Deakin J.A.
        • Mizuno K.
        • et al.
        Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.
        J Biol Chem. 1994; 269: 11216
        • MacDonald R.A.
        “Lifespan” of liver cells.
        Arch Intern Med. 1961; 107: 335
        • Malizia G.
        • Brunt E.M.
        • Peters M.G.
        • et al.
        Growth factor and procollagen type I expression in human liver disease.
        Gastroenterology. 1995; 108: 145
        • Mallat A.
        • Preaux A.
        • Blazejewski S.
        • et al.
        Interferon alfa and gamma inhibit proliferation and collagen synthesis of human Ito cells in culture.
        Hepatology. 1995; 21: 1003
        • Massague J.
        Transforming growth factor-alpha.
        J Biol Chem. 1990; 265: 21393
        • Massague J.
        Receptors of the TGF-β family.
        Cell. 1992; 69: 1067
        • Matsumoto K.
        • Tajima H.
        • Hamanoue M.
        • et al.
        Identification and characterization of “injurin,” an inducer of expression of the gene for hepatocyte growth factor.
        Proc Natl Acad Sci U S A. 1992; 89: 3800
        • Marti U.
        Handling of epidermal growth factor and the number of epidermal growth factor receptors are changed in aged male rats.
        Hepatology. 1993; 18: 1432
        • Masuhara M.
        • Katyal S.L.
        • Nakamura T.
        • et al.
        Differential expression of hepatocyte growth factor, transforming growth factor-a and transforming growth factor-βl messenger RNAs in two experimental models of liver cell proliferation.
        Hepatology. 1992; 16: 1241
        • Mead J.E.
        • Fausto N.
        Transforming growth factor α may be a physiological regulator of liver regeneration by means of an autocrine mechanism.
        Proc Natl Acad Sci U S A. 1989; 86: 1558
        • Milani S.
        • Grappone C.
        • Pellegrini G.
        • et al.
        Undulin RNA and protein expression in normal and fibrotic human liver.
        Hepatology. 1994; 20: 908
        • Miyazawa K.
        • Shimomura T.
        • Naka D.
        • et al.
        Proteolytic activation of hepatocyte growth factor in response to tissue injury.
        J Biol Chem. 1994; 269: 8966
        • Morita M.
        • Watanabe Y.
        • Akaike T.
        Protective effect of hepatocyte growth factor on interferon-gamma-induced cytotoxicity in mouse hepatocytes.
        Hepatology. 1995; 21: 1585
        • Nagy P.
        • Evarts R.P.
        • McMahon J.B.
        • et al.
        Role of TGF-beta in normal differentiation and oncogenesis in rat liver.
        Mol Carcinog. 1989; 2: 345
        • Nagy P.
        • Bisgaard H.C.
        • Thorgeirsson S.S.
        Expression of hepatic transcription factors during liver development and oval cell differentiation.
        J Cell Biol. 1994; 126: 223
        • Nakamura T.
        • Arakaki R.
        • Ichihara A.
        Interleukin-1 beta is a potent growth inhibitor of adult rat hepatocytes in primary culture.
        Exp Cell Res. 1988; 179: 488
        • Nishiguchi S.
        • Kuroki T.
        • Nakatani S.
        • et al.
        Randomised trial of effects of interferon-a on incidence of hepatocellular carcinoma in chronic active hepatitis C with cirrhosis.
        Lancet. 1995; 346: 1051
        • Oberhammer P.A.
        • Pavelka M.
        • Sharma S.
        • et al.
        Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor βl.
        Proc Natl Acad Sei U S A. 1992; 89: 5408
        • Ogasawara W.
        • Watanabe-Fukunuga R.
        • Adachi M.
        • et al.
        Lethal effect of anti-fas antibody in mice.
        Nature. 1993; 364: 806
        • Phillips M.
        • Poucell S.
        Modern aspects of the morphology of viral hepatitis.
        Hum Pathol. 1981; 12: 1060
        • Pinzani M.
        • Gentilini A.
        • Caliguiri A.
        • et al.
        Transforming growth factor-βl regulates platelet-derived growth factor receptor β subunit in human liver fat storing cells.
        Hepatology. 1995; 21: 232
        • Polimeno L.
        • Azzarone A.
        • Zeng Q.H.
        • et al.
        Cell proliferation and oncogene expression after bile duct ligation in the rat: Evidence of specific growth effect on bile duct cells.
        Hepatology. 1995; 21: 1070
        • Rana B.
        • Mischoulon D.
        • Xie Y.
        • et al.
        Cell-extracellular matrix interactions can regulate the switch between growth and differentiation in rat hepatocytes: Reciprocal expression of C/EBPa and immediate-early growth response transcription factors.
        Mol Cell Biol. 1994; 14: 5858
        • Rojkind M.
        • Greenwel P.
        The extracellular matrix of the liver.
        in: Arias IM Boyer JL Fausto N The Liver: Biology and Pathobiology. ed 3. Raven Press, New York1994: 843
        • Roskams T.
        • Moshage H.
        • De Vos R.
        • et al.
        Heparan sulfate proteoglycan expression in normal human liver.
        Hepatology. 1995; 21: 950
        • Rubin E.M.
        • Martin A.A.
        • Thung S.N.
        • et al.
        Morphometric and immunohistochemical characterization of human liver regeneration.
        Am J Pathol. 1995; 147: 397
        • Sakamoto S.
        • Yachi A.
        • Anzai T.
        AFP producing cells in hepatitis and in liver cirrhosis.
        Ann NY Acad Sei. 1975; 259: 253
        • Sanderson N.
        • Factor V.
        • Nagy P.
        • et al.
        Hepatic expression of mature transforming growth factor βl in transgenic mice results in multiple tissue lesions.
        Proc Natl Acad Sci U S A. 1995; 92: 2572
        • Sato Y.
        • Tsukada K.
        • Matsumoto Y.
        • et al.
        Interferon-7 inhibits liver regeneration by stimulating major histocompatibility complex class II antigen expression by regenerating liver.
        Hepatology. 1993; 18: 340
        • Schaffner F.
        Structural and functional aspects of regeneration of human liver.
        Dig Dis Sei. 1991; 56: 1282
        • Sell S.
        • Pierce G.B.
        Biology of disease. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers.
        Lab Invest. 1994; 70: 6
        • Shinozuka H.
        • Kubo Y.
        • Katyal S.L.
        • et al.
        Roles of growth factors and of tumor necrosis factor-a on liver cell proliferation induced in rats by lead nitrate.
        Lab Invest. 1994; 71: 35
        • Shiota G.
        • Okano J.
        • Kawasaki H.
        • et al.
        Serum hepatocyte growth factor levels in liver diseases: Clinical implications.
        Hepatology. 1995; 21: 106
        • Shiota G.
        • Nakamura T.
        • Schmidt E.V.
        Hepatocyte growth factor regulates transforming growth factor alpha in HepG2 hepatic cells.
        Biochem Biophys Res Commun. 1994; 200: 1099
        • Shiota G.
        • Wang T.C.
        • Nakamura T.
        • et al.
        Hepatocyte growth factor in transgenic mice: Effects on hepatocyte growth, liver regeneration and gene expression.
        Hepatology. 1994; 19: 962
        • Shiota G.
        • Rhoads D.B.
        • Wang T.C.
        • et al.
        Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells.
        Proc Natl Acad Sci U S A. 1992; 89: 373
        • Simpson G.E.C.
        • Finckh E.S.
        Pattern of regeneration of rat liver after repeated partial hepatectomies.
        J Pathol Bacteriol. 1963; 86: 361
        • Slott P.A.
        • Liu M.H.
        • Tavoloni N.
        Origin, pattern, and mechanism of bile duct proliferation following biliary obstruction in the rat.
        Gastroenterology. 1990; 99: 466
        • Suou T.
        • Hosho K.
        • Kishimoto Y.
        • et al.
        Long-term decrease in serum N-terminal propeptide of type III procollagen in patients with chronic hepatitis C treated with interferon alfa.
        Hepatology. 1995; 22: 426
        • Tartaglia A.L.
        • Ayres T.M.
        • Wong G.H.W.
        • et al.
        A novel domain within the 55 kD TNF receptor signals cell death.
        Cell. 1993; 74: 845
        • Thorgeirsson S.S.
        Hepatic stem cells.
        Am J Pathol. 1993; 142: 1331
        • Toyonaga T.
        • Hino O.
        • Sugai S.
        • et al.
        Chronic active hepatitis in transgenic mice expressing interferon-y in the liver.
        Proc Natl Acad Sei U S A. 1994; 91: 614
        • Tremble P.M.
        • Lane T.F.
        • Sage E.H.
        • et al.
        SPARC, a secreted protein associated with morphogenesis and tissue remodelling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway.
        J Cell Biol. 1993; 121: 1433
        • Tsukuma H.
        • Hiyama T.
        • Tanaka S.
        • et al.
        Risk factors for hepatocellular carcinoma among patients with hepatocellular carcinoma.
        N Engl J Med. 1993; 328: 1797
        • Vandersteenhoven A.M.
        • Burchette J.
        • Michalopoulos G.
        Characterization of ductular hepatocytes in end-stage cirrhosis.
        Arch Pathol Lab Med. 1990; 114: 403
        • Vassali P.
        The pathophysiology of tumor necrosis factors.
        Annu Rev Immunol. 1992; 10: 411
        • Volpes R.
        • Oors JJdv
        • De Vos R.
        • et al.
        Expression of interferon-y receptor in normal and pathological human liver tissue.
        J Hepatol. 1991; 12: 195
        • Wong S.T.
        • Winchell L.F.
        • McCune B.K.
        • et al.
        The TGF-a precursor expressed on the cell surface binds to the EGF receptor on adjacent cells leading to signal transduction.
        Cell. 1989; 56: 495
        • Yayon A.
        • Klagsbrun M.
        • Esko J.D.
        • et al.
        Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
        Cell. 1991; 64: 841
        • Yeh Y.C.
        • Tsai J.F.
        • Chuang L.Y.
        • et al.
        Elevation of transforming growth factor α and its relationship to epidermal growth factor and α-fetoprotein levels in patients with hepatocellular carcinoma.
        Cancer Res. 1987; 47: 896
        • Yoshioka K.
        • Kakumu S.
        • Arao M.
        • et al.
        Tumor necrosis factor-alpha production by peripheral blood mononuclear cells of patients with chronic liver disease.
        Hepatology. 1989; 10: 769
        • Zarnegar R.
        • Michalopoulos G.K.
        The many faces of hepatocyte growth factor: From hepatopoiesis to hematopoiesis.
        J Cell Biol. 1995; 129: 1177
        • Zarnegar R.
        • DeFrance M.C.
        • Kost D.P.
        • et al.
        Expression of hepatocyte growth factor in regenerating liver after partial hepatectomy.
        Biochem Biophys Res Commun. 1991; 177: 559

      Article info

      Identification

      DOI: https://doi.org/10.1016/S0272-2712(18)30272-5

      Copyright

      © 1996 Elsevier Inc. Published by Elsevier Inc. All rights reserved.

      ScienceDirect

      Access this article on ScienceDirect

      The content on this site is intended for healthcare professionals.


      We use cookies to help provide and enhance our service and tailor content. To update your cookie settings, please visit the Cookie Preference Center for this site.
      Copyright © 2023 Elsevier Inc. except certain content provided by third parties.


      RELX