• 1
    Tsukamoto H, Matsuoka M, French SW. Experimental models of hepatic fibrosis: an overview. Semin Liver Dis 1990; 10:5665.
  • 2
    Williams AO, Knapton AD. Hepatic silicosis, cirrhosis and liver tumors in mice and hamsters: studies of transforming growth factor β expression. Hepatology 1996; 23:12681275.
  • 3
    Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med 1994; 1:12861292.
  • 4
    Friedmann SL. Cytokines and fibrogenesis. Semin Liver Dis 1999; 19:129140.
  • 5
    Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 1986; 83:41674171.
  • 6
    Gebhardt R. Oxidative stress, plant-derived antioxidants and liver fibrosis. Planta Med 2002; 68:289296.
  • 7
    Milani S, Herbst H, Schuppan D, Hahn EG, Stein H. In situ hybridization for procollagen types I, II and IV mRNA in normal and fibrotic rat liver: evidence for predominant expression in nonparenchymal liver cells. Hepatology 1989; 10:8492.
  • 8
    Milani S, Herbst H, Schuppan D, Grappone C, Heinrichs OE. Cellular sources of extracellular matrix proteins in normal and fibrotic liver. Studies of gene expression by in situ hybridization. J Hepatol 1995; 22(Suppl):7176.
  • 9
    Gressner AM, Bachem MD. Cellular sources of noncollagenous matrix proteins: role of fat-storing cells in fibrogenesis. Semin Liver Dis 1993; 10:3046.
  • 10
    Sanderson N, Factor V, Nagy P, Kopp J, Kondaiah P, Wakefield L, Roberts AR, et al. Hepatic expression of mature transforming growth factor β1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci U S A 1995; 92:25722576.
  • 11
    Clouthier DE, Comerford SA, Hammer RE. Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGFβ1 transgenic mice. J Clin Invest 1997; 100:26972713.
  • 12
    Kanzler S, Lohse WA, Keil A, Henninger J, Dienes HP, Schirmacher P, Rose-John S, et al. TGF-β1 in liver fibrosis: an inducible transgenic mouse model to study liver fibrogenesis. J Physiol 1999; 276:G1059G1068.
  • 13
    Nolan JP. Endotoxin, reticuloendothelial function, and liver injury. Hepatology 1981; 1:458465.
  • 14
    Czaja MJ, Xu J, Ju Y, Alt E, Schmiedeberg P. Lipopolysaccharide-neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration. Hepatology 1994; 19:12821289.
  • 15
    Randow F, Syrbe U, Meisel C, Krausch D, Zuckernmann H, Platzer C. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J Exp Med 1995; 181:18871892.
  • 16
    Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline- responsive promoters. Proc Natl Acad Sci U S A 1992; 89:55475551.
  • 17
    Baron U, Bujard H. Tet repressor-based system for regulated gene expression in eukaryotic cells: principles and advances. Methods Enzymol 2000; 327:401421.
  • 18
    Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lubbert H, Bujard H. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci U S A 1996; 93:1093310938.
  • 19
    Schönig K, Bujard H. Generating conditional mouse mutants via tetracycline controlled gene expression. In: van DeusenJ, Hofker M, eds. The Transgenic Mouse: Methods and Protocols. New York: The Humana Press Inc., 2002.
  • 20
    Gossen M, Bujard H. Tetracyclines in the control of gene expression in eukaryotes. In: NelsonM, HillenW, GreenwaldRA, eds. Tetracyclines in Biology, Chemistry and Medicine Basel: Birkhäuser Verlag, 2001;139157.
  • 21
    Baron U, Freundlieb S, Gossen M, Bujard H. Co-regulation of two gene activities by tetracycline via a bidirectional promoter. Nucleic Acids Res 1995; 23:36053606.
  • 22
    Brunner AM, Marquardt H, Malacko AR, Lioubin MN, Purchio F. Site-directed mutagenesis of cystein residues in the pro region of the transforming growth factor β1 precursor. J Biol Chem 1989; 264:1366013664.
  • 23
    Samuel SK, Hurta RA, Kondaiah P, Khalil N, Turley EA, Wright JA, Greenberg AH. Autocrine induction of tumor protease production and invasion by a metallothionein-regulated TGF-beta 1 Ser223, 225. EMBO J 1992; 11:15991605.
  • 24
    Löw R, Rausch TH. Nonradioactive detection of nucleic acids with biotinylated probes. In: MeierT, SaluzHP, eds. A Laboratory Guide to Biotin Labelling in Biomolecule Analysis. Volume 7. Basel: Birkhäuser Verlag, 1996;201213.
  • 25
    Kistner A. Ph.D. Etablierung Tetrazyklin-kontrollierter Expressionssysteme in transgenen Mäusen. Thesis, Heidelberg, Germany: Universität Heidelberg, 1996.
  • 26
    Ueberham U, Ueberham E, Haustein UF, Herrmann K. Modulation of interstitial collagenase in scleroderma and normal fibroblasts. Eur J Dermatol 1996; 6:555562.
  • 27
    Jamall SI, Finelli VN, Hee SQ. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues. Anal Biochem 1981; 112:7075.
  • 28
    Shull MM, Doetschmann T. Transforming growth factor-beta1 in reproduction and development. Mol Reprod Develop 1994; 39:239246.
  • 29
    Arthur MJ. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am J Physiol 2000; 279:G245G249.
  • 30
    Eickelberg O. Endless healing: TGF-β, SMADs, and fibrosis. FEBS Lett 2001; 506:1114.
  • 31
    Bright JJ, Kerr LD, Sriram S. TGF-beta inhibits IL-2-induced tyrosine phosphorylation and activation of Jak-1 and Stat 5 in T-lymphocytes. J Immunol 1997; 159:175183.
  • 32
    Oberhammer FA, Pavelka M, Sharma S, Tiefenbacher R, Purchio AF, Bursch W, Schulte-Hermann R. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor β1. Proc Natl Acad Sci U S A 1992; 89:54085412.
  • 33
    Schrum LW, Bird AM, Salcher O, Burchardt E-R, Grisham JW, Brenner DA, Rippe AR, et al. Autocrine expression of activated transforming growth factor-β1 induces apoptosis in normal rat liver. Am J Physiol 2001; 280:G139G148.
  • 34
    Nakamura T, Tomita Y, Hirai R, Yamaoka K, Kaji K, Ichihara A. Inhibitory effect of transforming growth factor-beta on DNA synthesis of adult rat hepatocytes in primary culture. Biochem Biophys Res Commun 1985; 133:10421050.
  • 35
    Benyon RC, Iredale JP. Is liver fibrosis reversible? Gut 2000; 46:443446.
  • 36
    Gressner AM. Transdifferentiation of hepatic stellate (Ito) cells to myofibroblasts: a key event in hepatic fibrogenesis. Kidney Int 1996; 49:3945.
  • 37
    Knittel T, Mehde M, Kobold D, Saile B, Dinter C, Ramadori G. Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and non-parenchymal cells of rat liver: regulation by TNF-alpha and TGF-beta1. J Hepatol 1999; 30:4860.
  • 38
    Qi Z, Atsuchi N, Ooshima A, Takeshita A, Ueno H. Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat. Proc Natl Acad Sci U S A 1999; 96:23452349.
  • 39
    George J, Roulot D, Koteliansky VE, Bissell DM. In vivo inhibition of rat stellate cell activation by soluble transforming growth factor beta type II receptor: a potential new therapy for hepatic fibrosis. Proc Natl Acad Sci U S A 1999; 96:1271912724.
  • 40
    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; 35:10221030.
  • 41
    Benyon RC, Arthur JP. Extracellular matrix degradation and the role of hepatic stellate cells. Semin Liver Dis 2001; 21:373384.
  • 42
    Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, Hovell C, 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; 102:538549.
  • 43
    Yoshiji H, Kuriyama S, Miyamoto Y, Thorgeirsson UP, Gomez DE, Kawata M, Yoshii J, et al. Tissue inhibitor of metalloproteinases-1 promotes liver fibrosis development in a transgenic mouse model. Hepatology 2000; 32:12481254.
  • 44
    Arthur MJ. Matrix degradation in liver: a role in injury and repair. Hepatology 1997; 26:10691071.
  • 45
    Kossakowska AE, Edwards DR, Lee SS, Urbanski LS, Stabbler AL, Zhang CL, Phillips BW, et al. Altered balance between matrix metalloproteinases and their inhibitors in experimental biliary fibrosis. Am J Pathol 1998; 153:18951902.
  • 46
    Knittel T, Mehde M, Grundmann A, Saile B, Scharf JG, Ramadori G. Expression of matrix metalloproteinases and their inhibitors during hepatic tissue repair in the rat. Histochem Cell Biol 2000; 113:443453.
  • 47
    Winwood PJ, Schuppan D, Iredale JP, Kawser CA, Docherty AJ, Arthur MJ. Kupffer cell-derived 95-kd type IV collagenase/gelatinase B: characterization and expression in cultured cells. Hepatology 1995; 22:304315.