Liver extracellular matrix in health and disease

Journal of Pathology

Volumn 200, Issue 4, 2003, Pages 504-515

  Bedossa, Pierre ^a   Paradis, Valérie ^b  

^a BICÊTRE HOSPITAL   (France)

^b BEAUJON HOSPITAL   (France)

Author keywords

Cirrhosis; Extracellular matrix; Fibrosis; Fibrosis regression; Hepatic stellate cell; Liver biopsy

Indexed keywords

ALPHA TOCOPHEROL; BETA INTERFERON; DIMETHYL SULFOXIDE; ENDOTHELIN 1; ENZYME INHIBITOR; FUMAGILLOL CHLOROACETYLCARBAMATE; GAMMA INTERFERON; GROWTH FACTOR; HALOFUGINONE; INTERLEUKIN 10; PLATELET DERIVED GROWTH FACTOR; PROCOLLAGEN PROLINE 2 OXOGLUTARATE 4 DIOXYGENASE; PROTEIN ANTIBODY; RESVERATROL; SILYMARIN; TRANSFORMING GROWTH FACTOR BETA1;

BLOOD FLOW; CELL ACTIVATION; CELL ISOLATION; DISEASE COURSE; DRUG MECHANISM; EXTRACELLULAR MATRIX; FIBROGENESIS; HEPATITIS C; HUMAN; LIVER BIOPSY; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER FIBROSIS; LIVER FUNCTION; LIVER STRUCTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REMISSION; REVIEW; STELLATE CELL;

ANTIBODIES, MONOCLONAL; CELL ADHESION; CELL DIVISION; DISEASE PROGRESSION; EXTRACELLULAR MATRIX; GROWTH SUBSTANCES; HEPATOCYTES; HUMANS; LIVER; LIVER CIRRHOSIS; REGENERATION; TELOMERASE;

EID: 0037899248     PISSN: 00223417     EISSN: None     Source Type: Journal    
DOI: 10.1002/path.1397     Document Type: Review

References (114)

1. Martinez Hernandez A, Amenta PS. Morphology, localization and origin of the hepatic extracellular matrix. In Extracellular Matrix, Chemistry, Biology and Pathobiology with Emphasis on the Liver, Zern MA, Reid LM (eds). Marcel Dekker: New York, 1993; 201-254.
2. Schuppan D. Structure of the extracellular matrix in normal and fibrotic liver: collagens and glycoproteins. Semin Liver Dis 1990; 10: 1-10.
3. Gressner AM. Hepatic fibrogenesis: the puzzle of interacting cells, fibrogenic cytokines, regulatory loops and extracellular matrix molecules. Z Gastroenterol (Suppl 1) 1992; 30: 5-16.
4. Friedman SL. The cellular basis of hepatic fibrosis: mechanism and treatment strategies. N Engl J Med 1993; 328: 1828-1835.
5. Albanis E, Friedman SL. Hepatic fibrosis: pathogenesis and principles of therapy. Clin Liver Dis 2001; 5: 315-334.
6. Bedossa P, Paradis V. Approaches for treatment of liver fibrosis in chronic hepatitis C. Clin Liver Dis 2003; 7: 1-17.
7. Lin XZ, Horng MH, Sun YN, Shiesh SC, Chow NH, Guo XZ. Computer morphometry for quantitative measurement of liver fibrosis: comparison with Knodell's score, colorimetry and conventional description reports. J Gastroenterol Hepatol 1998; 13: 75-80.
8. Rojkind M, Giambrone MA, Biempica L. Collagen types in normal and cirrhotic liver. Gastroenterology 1985; 76: 710-719.
9. Schuppan D, Cramer T, Bauer M, Strefeld T, Hahn EG, Herbst H. Hepatocytes as a source of collagen type XVIII endostatin. Lancet 1998; 352: 879-880.
10. Martinez-Hernandez A. The hepatic extracellular matrix. I. Electron immunohistochemical studies in normal rat liver. Lab Invest 1984; 51: 57-74.
11. 4-induced cirrhosis. Lab Invest 1985; 53: 166-186.
12. Bissel M, Caron JM, Babiss LE, Friedman S. Transcriptional regulation of the albumin gene in cultured rat hepatocytes: role of basement-membrane matrix. Mol Biol Med 1990; 7: 187 -197.
13. Gressner AM. Hepatic proteoglycans: a brief survey of their pathobiochemical implications. Hepato-Gastroenterol 1983; 30: 225-229.
14. McGuire RF, Bissell DM, Boyles J, Roll FJ. Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver. Hepatology 1992; 15: 989-997.
15. Schaffner F, Popper H. Capillarization of the sinusoids in man. Gastroenterology 1963; 44: 239-242.
16. Friedman SL, Roll FJ, Boyles J, Arenson DM, Bissell DM. Maintenance of differentiated phenotype of cultured rat hepatic lipocytes by basement membrane matrix. J Biol Chem 1989; 264: 10756-10762.
17. Somasundaram R, Schuppan D. Type I, II, III, IV, V, and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (AA, BB, and AB). J Biol Chem 1996; 271: 26884-26891.
18. Ramadori G, Saile B. Mesenchymal cells in the liver: one cell type or two? Liver 2002; 22: 283-294.
19. Corpechot C, Barbu V, Wendum D, et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 2002; 35: 1010-1021.
20. Bhunchet E, Fujieda K. Capillarization and venularization of hepatic sinusoids in porcine serum-induced rat liver fibrosis: a mechanism to maintain liver blood flow. Hepatology 1993; 18: 1450-1458.
21. Li D, Friedman S. Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy. J Gastroenterol Hepatol 1999; 14: 618-633.
22. Friedman SL. Hepatic stellate cells. Prog Liver Dis 1996; 14: 101-130.
23. Bedossa P. The cell origin of extracellular matrix proteins. J Hepatol 1993; 19: 1-3.
24. Friedman SL, Roll FJ. Isolation and culture of hepatic lipocytes, kupffer cells, and sinusoidal endothelial cells by density gradient centrifugation with Stractan. Anal Biochem 1987; 161: 1233-1247.
25. Eng FJ, Friedman SL, Fibrogenesis I. New insights into hepatic stellate cell activation: the simple becomes complex. Am J Physiol Gastrointest Liver Physiol 2000; 279: G7 -G11.
26. Knittel T, Kobold D, Saile B, et al. Rat liver myofibroblasts and hepatic stellate cells: different cell populations of the fibroblast lineage with fibrogenic potential. Gastroenterology 1999; 117: 1205-1221.
27. Wake K. Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes) their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 1980; 66: 303-353.
28. Bronfenmajer S, Schaffner F, Popper H. Fat-storing cells (lipocytes) in human liver. Arch Pathol 1966; 82: 447-453.
29. Pinzani M. Liver fibrosis. Springer Semin Immunopathol 2000; 21: 475-490.
30. Blomhoff R, Green MH, Berg T, Norum KR. Transport and storage of vitamin A. Science 1990; 250: 399-404.
31. Pinzani M, Failli P, Ruocco C, et al. Fat-storing cells as liver-specific pericytes: spatial dynamics of agonist-stimulated intracellular calcium transient. J Clin Invest 1992; 90: 642-646.
32. Dubuisson L, Desmouliere A, Decourt B, et al. Inhibition of rat liver fibrogenesis through noradrenergic antagonism. Hepatology 2002; 35: 325-331.
33. Neubauer K, Knittel T, Aurisch S, Fellmer P, Ramadori G. Glial fibrillary acidic protein: a cell type specific marker for Ito cells in vivo and in vitro. J Hepatol 1996; 24: 719-730.
34. Bedossa P, Paradis V, Dargere D, Bonvoust F, Vidaud M. Dystroglycan expression in hepatic stellate cells. Lab Invest 2002; 82: 1053-1061.
35. Knittel T, Aurisch S, Neubauer K, Eichhorst S, Ramadori G. Cell-type-specific expression of neural cell adhesion molecule (NCAM) in Ito cells of rat liver. Am J Pathol 1996; 149: 449-462.
36. 4-cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin-43. Lab Invest 1993; 69: 210-216.
37. Friedman SL, Arthur MJ. Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium: direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors. J Clin Invest 1989; 84: 1780-1785.
38. Gressner AM. Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: a key event in hepatic fibrogenesis. Kidney Int 1996; 54: S39-S45.
39. Ramadori G, Veilt T, Schwogler S, et al. Expression of the gene of the a-smooth muscle-actin isoform in rat liver and in rat fat storing (Ito) cells. Virchows Arch 1990; 59: 349-357.
40. Tsutsumi M, Takada A, Takase S. Characterization of desmin positive rat liver sinusoidal cells. Hepatology 1987; 7: 277-284.
41. Milani S, Herbst H, Schuppan D, et al. Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver. Am J Pathol 1994; 144: 528-537.
42. Kon K, Ikejima. K, Hirose M, et al. Pioglitazone prevents earlyphase hepatic fibrogenesis caused by carbon tetrachloride. Biochem Biophys Res Commun 2002; 291: 55-61.
43. Friedman S. Cytokines and fibrogenesis. Semin Liver Dis 1999; 19: 129-140.
44. Svegliati Baroni G, D'Ambrosio L, Ferretti G, et al. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology 1998; 27: 720-726.
45. Bacon BR, Britton RS. The pathology of hepatic iron overload: a free radical-mediated process? Hepatology 1990; 11: 127-137.
46. Paradis V, Mathurin P, Kollinger M, et al. In situ detection of lipid peroxidation in chronic hepatitis C: correlation with pathological features. J Clin Pathol 1997; 50: 401-406.
47. Poli G. Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med 2000; 21: 49-98.
48. Maher JJ, Tzagarakis C, Gimenez A. Malondialdehyde stimulates collagen production by hepatic lipocytes only upon activation in primary culture. Alcohol Alcohol 1994; 29: 605-610.
49. Jarnagin WR, Rockey DC, Koteliansky VE, Wang SS, Bissell DM. Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis. J Cell Biol 1994; 127: 2037-2048.
50. Ratziu V, Lalazar A, Wong L, et al. Zf9, a Kruppel-like transcription factor up-regulated in vivo during early hepatic fibrosis. Proc Natl Acad Sci USA 1998; 95: 9500-9505.
51. Mann DA, Smart DE. Transcriptional regulation, of hepatic stellate cell activation. Gut 2002; 50: 891-896.
52. Pinzani M, Gesualdo L, Sabbah GM, Abboud HE. Effects of platelet-derived growth factor and other polypeptide mitogens on DNA synthesis and growth of cultured rat liver fat-storing cells. J Clin Invest 1989; 84: 1786-1793.
53. Wong L, Yamasaki G, Johnson RJ, Friedman SL. Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. J Clin Invest 1994; 94: 1563-1569.
54. Carloni V, Pinzani M, Giusti S, et al. Tyrosine phosphorylation of focal adhesion kinase by PDGF is dependent on ras in human hepatic stellate cells. Hepatology 2000; 31: 131-140.
55. Yoshiji H, Kuriyama S, Yoshii J, et al. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology 2001; 34: 745-750.
56. Bataller R, Nicolas JP, Gines P, et al. Arginine vasopressin induces contraction and stimulates growth of cultured human hepatic stellate cells. Gastroenterology 1997; 113: 615-624.
57. Pinzani M, Gentilini P. Biology of hepatic stellate cells and their possible relevance in the pathogenesis of portal hypertension in cirrhosis. Semin Liver Dis 1999; 19: 397-410.
58. Gressner AM, Weiskirchen R, Breitkopf K, Dooley S. Roles of TGF-beta in hepatic fibrosis: roles of TGF-beta in hepatic fibrosis. Front Biosci 2002; 7: 793-807.
59. Dallas SL, Miyazono K, Skerry TM, Mundy GR, Bonewald LF. Dual role for the latent transforming growth factor-beta binding protein in storage of latent TGF-beta in the extracellular matrix and as a structural protein. J Cell Biol 1995; 131: 539-549.
60. Crawford SE, Stellmach V. Murphy-Ullrich JE, et al. Thrombospondin-1 is a major activator of TGF-β1 in vivo. Cell 1998; 93: 1159-1170.
61. Casini A, Pinzani M, Milani S, et al. Regulation of extracellular matrix synthesis by transforming growth factor β-1 in human fat storing cells. Gastroenterology 1993; 105: 245-253.
62. Heldin CH, Miyazono K, Dijke P. TGF beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390: 465-471.
63. Paradis V, Dargere D, Vidaud M, et al. Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology 1999; 30: 968-976.
64. Bradham DM, Igarashi A, Potter RL, Grotendorst GR. Connective tissue growth factor: a cysteine-rich mitogen secreted by human vascular endothelial cells is related to the SRC-induced immediate early gene product CEF-10. J Cell Biol 1991; 114: 1285-1294.
65. Grotendorst GR, Okochi H, Hayashi N. A novel transforming growth factor beta response element controls the expression of the connective tissue growth factor gene. Cell Growth Differ 1996; 7: 469-480.
66. Lichtinghagen R, Michels D, Haberkorn CI, et al. Matrix metalloproteinase (MMP)-2, MMP-7, and tissue inhibitor of metalloproteinase-1 are closely related to the fibroproliferative process in the liver during chronic hepatitis C. J Hepatol 2001; 34: 239-247.
67. Kim BC, Mamura M, Choi KS, Calabretta B, Kim SJ. Transforming growth factor beta 1 induces apoptosis through cleavage of BAD in a Smad3-dependent mechanism in FaO hepatoma cells. Mol Cell Biol 2002; 22: 1369-1378.
68. Ikejima K, Takei Y, Honda H, et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 2002; 122: 1399-1410.
69. Housset C, Rockey DC, Bissell DM. Endothelin receptors in rat liver: lipocytes as a contractile target for endothelin 1. Proc Natl Acad Sci USA 1993; 90: 9266-9270.
70. Kawada N, Tran-Thi TA, Klein H, Decker K. The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances: possible involvement of endothelin 1 and nitric oxide in the regulation of sinusoidal tonus. Eur J Biochem 1993; 213: 815-823.
71. Marra F, Valente AJ, Pinzani M, Abboud HE. Cultured human liver fat-storing cells produce monocyte chemotactic protein 1: regulation by proinflammatory cytokines. J Clin Invest 1993; 92: 1674-1680.
72. Bonacchi A, Romagnani P, Romanelli RG, et al. Signal transduction by the chemokine receptor CXCR3: activation of Ras/ERK, Src, and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes. J Biol Chem 200 1; 276: 9945 -9954.
73. Wang SC, Ohata M, Schrum L, Rippe RA, Tsukamoto H. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J Biol Chem 1998; 273: 302-308.
74. Boros DL, Whitfield JR. Enhanced Th1 and dampened Th2 responses synergize to inhibit acute granulomatous and fibrotic responses in murine schistosomiasis mansoni. Infect Immun 1999; 67: 1187-1193.
75. Carloni V, Romanelli RG, Pinzani M, Laffi G, Gentilini P. Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells. Gastroenterology 1996; 100: 1127-1136.
76. Olaso E, Ikeda K, Eng FJ, et al. DDR2 receptor promotes MMP2-mediated proliferation and invasion by hepatic stellate cells. J Clin Invest 2001; 108: 1369-1378.
77. Knodell KG, Ishak KG, Black WC. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431-435.
78. Bedossa P. and the METAVIR Group. Intra- and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. Hepatology 1994; 20: 15-20.
79. Pilette C, Rousselet MC, Bedossa P, et al. Histopathological evaluation of liver fibrosis: quantitative image analysis vs semiquantitative scores. Comparison with serum markers. J Hepatol 1998; 28: 439-446.
80. Walsh KM, Timms P, Campbell S, MacSween RN, Morris AJ. Plasma levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases -1 and -2 (TIMP-1 and TIMP2) as noninvasive markers of liver disease in chronic hepatitis C: comparison using ROC analysis. Dig Dis Sci 1999; 44: 624-630.
81. Imbert-Bismut F, Ratziu V, Pieroni L, Charlotte F, Benhamou Y, Poynard T. MULTIVIRC group biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet 2001; 357: 1069-1075.
82. Fontana RJ, Lok AS. Noninvasive monitoring of patients with chronic hepatitis C. Hepatology 2002; 36: S57-S64.
83. Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis c. J Hepatol. 2001; 34: 730-739.
84. Poynard T, Bedossa P, Opolon P, for the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997; 349: 825-832.
85. Benhamou Y, Di Martino V, Bochet M, et al. Factors affecting liver fibrosis in human immunodeficiency virus- and hepatitis C virus-coinfected patients: impact of protease inhibitor therapy. Hepatology 2001; 34: 283-287.
86. Powell EE, Edwards-Smith CJ, Hay JL, et al. Host genetic factors influence disease progression in chronic hepatitis C. Hepatology 2000; 31: 828-833.
87. Hillebrandt S, Goos C, Matern S, Lammert F. Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfibl on chromosome 15. Gastroenterology 2002; 123: 2041-2051.
88. Wanless IR, Nakashima E, Sherman M. Regression of human cirrhosis: morphologic features and the genesis of incomplete septal cirrhosis. Arch Pathol Lab Med 2000; 124: 1599-1607.
89. Iredale JP, Benyon RC, Pickering J, et al. Mechanisms of spontaneous resolution of rat liver fibrosis: hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 1998; 102: 538-549.
90. Hammel P, Couvelard A, O'Toole D, et al. Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct. N Engl J Med 2001; 344: 452-454.
91. Poynard T, McHutchison J, Manns M, et al. Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 2002; 122: 1303-1313.
92. Shiratori Y, Imazeki F, Moriyama M, et al. Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann Intern Med 2000; 132: 517-524.
93. Arthur MI. Collagenases and liver fibrosis. J Hepatol 1995; 22: 43-48.
94. Arthur MJ, Stanley A, Iredale JP, Rafferty JA, Hembry RM, Friedman SL. Secretion of 72 kDa type IV collagenase/gelatinase by cultured human lipocytes: analysis of gene expression, protein synthesis and proteinase activity. Biochem J 1992; 287: 701-707.
95. Théret N, Musso O, Lhelgoualch A, Clement B. Activation of matrix metalloproteinase-2 from hepatic stellate cells requires interactions with hepatocytes. Am J Pathol 1997; 150: 51-58.
96. Iredale JP, Benyon RC, Arthur MJ, et al. Tissue inhibitor of metalloproteinase-1 messenger RNA expression is enhanced relative to interstitial collagenase messenger RNA in experimental liver injury and fibrosis. Hepatology 1996; 24: 176-184.
97. Benyon RC, Iredale JP, Goddard S, Winwood PJ, Arthur MJ. Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver. Gastroenterology 1996; 110: 821-831.
98. Shrivastava A, Radziejewski C, Campbell E, et al. An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol Cell 1997; 1: 25-34.
99. Taimr P, Higuchi H, Kocova E, Rippe RA, Friedman S, Gores GJ. Activated stellate cells express the TRAIL receptor2/death receptor-5 and undergo TRAIL-mediated apoptosis. Hepatology 2003; 37: 87-95.
100. Saile B, Knittel T, Matthes N, Schott P, Ramadori G. CD95/Cd951-mediated apoptosis of the hepatic stellate cell: a mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair. Am J Pathol 1997; 151: 1265 -1272.
101. Fine A, Miranda K, Farmer SR, Anderson NL. Effect of insoluble extracellular matrix molecules on Fas expression in epithelial cells. J Cell Physiol 1998; 174: 285-292.
102. Hahn WC. Senescence, telomere shortening and telomere maintenance. Cancer Biol Ther 2002; 1: 398-400.
103. Paradis V, Youssef N, Dargere D, et al. Replicative senescence in normal liver, chronic hepatitis C, and hepatocellular carcinomas. Hum Pathol 2001; 32: 327-332.
104. Rudolph KL, Chang S, Millard M, Schreiber-Agus N, DePinho RA. Inhibition of experimental liver cirrhosis in mice by telomerase gene delivery. Science 2000; 287: 1185-1187.
105. Sobesky R, Mathurin P, Charlotte F, et al. Modeling the impact of interferon alfa treatment on liver fibrosis progression in chronic hepatitis C: a dynamic view. The Multivirc Group. Gastroenterology 1999; 116: 378-386.
106. Yata Y, Gotwals P, Koteliansky V, Rockey DC. Dose-dependent inhibition of hepatic fibrosis in mice by a TGF-beta soluble receptor: implications for antifibrotic therapy. Hepatology 2002; 35: 1022-1030.
107. McGaha TL, Phelps RG, Spiera H, Bona C. Halofuginone, an inhibitor of type-I collagen synthesis and skin sclerosis, blocks transforming-growth-factor-beta-mediated Smad3 activation in fibroblasts. J Invest Dermatol 2002; 118: 461-470.
108. Wang YQ, Ikeda K, Ikebe T, et al. Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats. Hepatology 2000; 32: 980-989.
109. Iwamoto H, Sakai H, Kotoh K, Nakamura M, Nawata H. Soluble Arg-Gly-Asp peptides reduce collagen accumulation in cultured rat hepatic stellate cells. Dig Dis Sci 1999; 44: 1038-1045.
110. Nakamura M, Ohta S, Tada S, et al. Dimethyl sulfoxide inhibits dimethylnitrosamine-induced hepatic fibrosis in rats. Int J Mol Med 2001; 8: 553-560.
111. Vendemiale G, Grattagliano I, Caruso ML, et al. Increased oxidative stress in dimethylnitrosamine-induced liver fibrosis in the rat: effect of N-acetylcysteine and interferon-alpha. Toxicol Appl Pharmacol 2001; 175: 130-139.
112. Chiaramonte MG, Cheever AW, Malley JD, Amichay D, Wynn TA, Farber JM. Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis. Hepatology 2001; 34: 273-282.
113. Bickel M, Baringhaus KH, Gerl M, et al. Selective inhibition of hepatic collagen accumulation in experimental liver fibrosis in rats by a new prolyl 4-hydroxylase inhibitor. Hepatology 1998; 28: 404-411.
114. Ueki T, Kaneda Y, Tsutsui H, et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat Med 1999; 5: 226-230.