Liver fibrogenesis and the role of hepatic stellate cells: New insights and prospects for therapy

Journal of Gastroenterology and Hepatology (Australia)

Volumn 14, Issue 7, 1999, Pages 618-633

  Li, Dan ^a   Friedman, Scott L ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

Anti fibrotic therapy; Cytokines; Extracellular matrix; Hepatic fibrosis; Hepatic stellate cells

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ANTIFIBROTIC AGENT; ANTIOXIDANT; ARGINYLGLYCYLASPARTIC ACID; COLCHICEINE; COLCHICINE; CORTICOSTEROID; CYTOKINE; CYTOKINE ANTIBODY; ENDOTHELIN RECEPTOR ANTAGONIST; GAMMA INTERFERON; HALOFUGINONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 10; LUFIRONIL; MATRIX METALLOPROTEINASE; PENTOXIFYLLINE; PROSTAGLANDIN E; QUERCETIN; RELAXIN; RESVERATROL; RETINOID; SILYMARIN; TISSUE INHIBITOR OF METALLOPROTEINASE; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TUMOR NECROSIS FACTOR ALPHA RECEPTOR; UNINDEXED DRUG; URSODEOXYCHOLIC ACID;

APOPTOSIS; BLAST TRANSFORMATION; CELL ACTIVATION; CYTOKINE RELEASE; DISEASE COURSE; DRUG TARGETING; EXTRACELLULAR MATRIX; FIBROGENESIS; LIVER CELL; LIVER CIRRHOSIS; LIVER FAILURE; LIVER FIBROSIS; LIVER INJURY; MYOFIBROBLAST; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; STELLATE CELL; TREATMENT PLANNING;

EID: 0032801286     PISSN: 08159319     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1440-1746.1999.01928.x     Document Type: Review

References (220)

1. 1 Friedman SL. Seminars in medicine of the Beth Israel Hospital, Boston. The cellular basis of hepatic fibrosis. Mechanisms and treatment strategies. N. Engl. J. Med. 1993; 328: 1828-35.
2. 2 Timpl R. Macromolecular organization of basement membranes. Curr. Opin. Cell Biol. 1996; 8: 618-24.
3. 3 Musso O, Rehn M, Saarela J et al. Collagen XVIII is localized in sinusoids and basement membrane zones and expressed by hepatocytes and activated stellate cells in fibrotic human liver. Hepatology 1998; 28: 98-107.
4. 4 Clement B, Musso O, Lietard J, Theret N. Homeostatic control of angiogenesis: A newly identified function of the liver? Hepatology 1999; 29: 621-3.
5. 5 Rescan PY, Loreal O, Hassell JR, Yamada Y, Guillouzo A, Clement B. Distribution and origin of the basement membrane component perlecan in rat liver and primary hepatocyte culture. Am. J. Pathol. 1993; 142: 199-208.
6. 6 Meyer DH, Krull N, Dreher KL, Gressner AM. Biglycan and decorin gene expression in normal and fibrotic rat liver: Cellular localization and regulatory factors. Hepatology 1992; 16: 204-16.
7. 7 Roskams T, Moshage H, De Vos R, Guido D, Yap P, Desmet V. Heparan sulfate proteoglycan expression in normal human liver. Hepatology 1995; 21: 950-8.
8. 8 Rojkind M, Giambrone MA, Biempica L. Collagen types in normal and cirrhotic liver. Gastroenterology 1979; 76: 710-19.
9. 9 Gressner AM, Bachem MG. Cellular sources of noncollagenous matrix proteins: Role of fat-storing cells in fibrogenesis. Semin. Liver Dis. 1990; 10: 30-46.
10. 10 Gressner AM, Bachem MG. Molecular mechanisms of liver fibrogenesis: A homage to the role of activated fat-storing cells. Digestion 1995; 56: 335-46.
11. 11 McGuire RF, Bissell DM, Boyles J, Roll FJ. Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver. Hapatology 1992; 15: 989-97.
12. 12 Arthur MJ. Fibrosis and altered matrix degradation. Digestion 1998; 59: 376-80.
13. 13 Takahara T, Furui K, Yata Y et al. Dual expression of matrix metalloproteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology 1997; 26: 1521-9.
14. 14 Vyas SK, Leyland H, Gentry J, Arthur MJ. Rat hepatic lipocytes synthesize and secrete transin (stromelysin) in early primary culture. Gastroenterology 1995; 109: 889-98.
15. 15 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: 528-37.
16. 16 Herbst H, Wege T, Milani S et al. Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis. Am. J. Pathol. 1997; 150: 1647-59.
17. 17 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: 821-31.
18. 18 Iredale JP, Goddard S, Murphy G, Benyon RC, Arthur MJ. Tissue inhibitor of metalloproteinase-I and interstitial collagenase expression in autoimmune chronic active hepatitis and activated human hepatic lipocytes. Clin. Sci. 1995; 89: 75-81.
19. 19 Iredale JP. Tissue inhibitors of metalloproteinases in liver fibrosis. Int. J. Biochem. Cell Biol. 1997; 29: 43-54.
20. 20 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: 176-84.
21. 21 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: 538-49.
22. 22 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: 701-7.
23. 23 Poulos JE, Baldassare JJ, Bacon BR et al. Fibronectin and cytokines increase JNK, ERK, AP-1 activity, and transin gene expression in rat hepatic stellate cells. Am. J. Physiol. 1997; 273: G804-11.
24. 24 Theret N, Musso O, L'Helgoualc'h A, Clement B. Activation of matrix metalloproteinase-2 from hepatic stellate cells requires interactions with heparocytes. Am. J. Pathol. 1997; 150: 51-8.
25. 25 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: 304-15.
26. 26 Arthur MJ. Collagenases and liver fibrosis. J. Hepatol. 1995; 22 (Suppl.): 43-8.
27. 27 Arenson DM, Friedman SL, Bissell DM. Formation of extracellular matrix in normal rat liver: Lipocytes as a major source of proteoglycan. Gastroenterology 1988; 95: 441-7.
28. 28 Maher JJ, Bissell DM, Friedman SL, Roll FJ. Collagen measured in primary cultures of normal rat hepatocytes derives from lipocytes within the monolayer. J. Clin. Invest. 1988; 82: 450-9.
29. 29 Milani S, Herbst H, Schuppan D, Kim KY, Riecken EO, Stein H. Procollagen expression by nonparenchymal rat liver cells in experimental biliary fibrosis. Gastroenterology 1990; 98: 175-84.
30. 30 Maher JJ, McGuire RF. Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo. J. Clin. Invest. 1990; 86: 1641-8.
31. 31 Pietrangelo A, Gualdi R, Geerts A, De Bleser P, Casalgrandi G, Ventura K. Enhanced hepatic collagen gene expression in a rodent model of hemochromatosis. Gastroenterology 1992; 102 (Suppl.): A868.
32. 32 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: 10 756-62.
33. 33 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: 2037-48.
34. 34 Gallai M, Kovalszky I, Knittel T, Neubauer K, Armbrust T, Ramadori G. Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured rat liver and in isolated liver cells. Am. J. Pathol. 1996; 148: 1463-71.
35. 35 Friedman SL. Cytokines and fibrogenesis. Semin. Liver Dis. 1999; 19: 129-40.
36. 36 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: 26884-91.
37. 37 Pinzani M, Marra F, Carloni V. Signal transduction in hepatic stellate cells. Liver 1998; 18: 2-13.
38. 38 Vogel W, Gish GD, Alves F, Pawson T. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol. Cell. 1997; 1: 13-23.
39. 39 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.
40. 40 Ankoma-Sey V, Matli M, Chang KB et al. Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 1998; 17: 115-21.
41. 41 Clark EA, Brugge JS. Integrins and signal transduction pathways: The road taken. Science 1995; 268: 233-9.
42. 42 Scoazec JY. Adhesion molecules in normal human liver. Hepatogastroenterology 1996; 43: 1103-5.
43. 43 Scoazec JY. Expression of cell-matrix adhesion molecules in the liver and their modulation during fibrosis. J. Hepatol. 1995; 22 (Suppl.): 20-7.
44. 44 Iredale JP, Arthur MJ. Hepatocyte-matrix interactions. Gut 1994; 35: 729-32.
45. 45 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; 110: 1127-36.
46. 46 Carloni V, Romanelli RG, Pinzani M, Laffi G, Gentilini P. Focal adhesion kinase and phospholipase C gamma involvement in adhesion and migration of human hepatic stellate cells. Gastroenterology 1997; 112: 522-31.
47. 47 Racine-Samson L, Rockey DC, Bissell DM. The role of alpha1beta1 integrin in wound contraction. A quantitative analysis of liver myofibroblasts in vivo and in primary culture. J. Biol. Chem. 1997; 272: 30 911-17.
48. 48 Imai K, Senoo H. Morphology of sites of adhesion between hepatic stellate cells (vitamin A-storing cells) and a three-dimensional extracellular matrix. Anat. Rec. 1998; 250: 430-7.
49. 49 Bruck R, Shirin H, Hershkoviz R et al. Analysis of Arg-Gly-Asp mimetics and soluble receptor of tumour necrosis factor as therapeutic modalities for concanavalin A induced hepatitis in mice. Gut 1997; 40: 133-8.
50. 50 Iwamoto H, Sakai H, Nawata H. Inhibition of integrin signaling with Arg-Gly-Asp motifs in rat hepatic stellate cells. J. Hepatol. 1998; 29: 752-9.
51. 51 Bronfenmajer S, Schaffner F, Popper H. Fat-storing cells (lipocytes) in human liver. Arch. Pathol. 1966; 82: 447-53.
52. 52 Giampieri MP, Jezequel AM, Orlandi F. The lipocytes in normal human liver. Digestion 1981; 22: 165-9.
53. 53 Jezequel AM, Novelli G, Venturini C, Orlandi F. Quantitative analysis of the perisinusoidal cells in human liver; the lipocytes. Front. Gastrointest. Res. 1984; 8: 85-90.
54. 4-induced fibrotic rat livers. Hepatology 1996; 23: 1538-45.
55. 55 Ballardini G, Groff P, Badiali dGL, Schuppan D, Bianchi FB. Ito cell heterogeneity: Desmin-negative Ito cells in normal rat liver. Hepatology 1994; 19: 440-6.
56. 56 Ramm GA, Britton RS, O'Neill R, Blaner WS, Bacon BR, Vitamin A-poor lipocytes: A novel desmin-negative lipocyte subpopulation, which can be activated to myofibroblasts. Am. J. Physiol. 1995; 269: G532-41.
57. 57 Ueno T, Sata M, Sakata R et al. Hepatic stellate cells and intralobular innervation in human liver cirrhosis. Hum. Pathol. 1997; 28: 953-9.
58. 58 Gressner AM. Transdifferentiation of hepatic stellate cells (Ito cells) to myofibroblasts: A key event in hepatic fibrogenesis. Kidney Int. 1996; 54 (Suppl.): S39-45.
59. 59 Okuno M, Moriwaki H, Imai S et al. Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-beta in liver stellate cells. Hepatology 1997; 26: 913-21.
60. 60 Gressner AM. Cytokines and cellular crosstalk involved in the activation of fat-storing cells. J. Hepatol. 1995; 22 (Suppl.): 28-36.
61. 61 Houglum K, Venkataramani A, Lyche K, Chojkier M. A pilot study of the effects of d-alpha-tocopherol on hepatic stellate cell activation in chronic hepatitis C. Gastroenterology 1997; 113: 1069-73.
62. 62 Houglum K, Bedossa P, Chojkier M. TGF-beta and collagen-alpha 1 (I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload. Am. J. Physiol. 1994; 267: G908-13.
63. 63 Leo MA, Rosman AS, Lieber CS. Differential depletion of carotenoids and tocopherol in liver disease. Hepatology 1993; 17: 977-86.
64. 64 Paradis V, Kollinger M, Fabre M, Holstege A, Poynard T, Bedossa P. In situ detection of lipid peroxidation byproducts in chronic liver diseases. Hepatology 1997; 26: 135-42.
65. 65 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: 401-6.
66. 66 Svegliati Baroni G, D'Ambrosio L, Ferretti G et al. Fibrogenic effect of oxidative stress on rat hepatic stellate cells. Hepatology 1998; 27: 720-6.
67. 67 Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb expression. J. Clin. Invest. 1995; 96: 2461-8.
68. 68 Hines JE, Johnson SJ, Burt AD. In vivo responses of macrophages and perisinusoidal cells to cholestatic liver injury. Am. J. Pathol. 1993; 142: 511-18.
69. 69 Matsuoka M, Tsukamoto H. Stimulation of hepatic lipocyte collagen production by Kupffer cell-derived transforming growth factor beta: Implication for a pathogenetic role in alcoholic liver fibrogenesis. Hepatology 1990; 11: 599-605.
70. 70 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: 1780-5.
71. 71 Enzan H, Himeno H, Iwamura S et al. Alpha-smooth muscle actin-positive perisinusoidal stromal cells in human hepatocellular carcinoma. Hepatology 1994; 19: 895-903.
72. 72 Enzan H, Himeno H, Iwamura S et al. Sequential changes in human Ito cells and their relation to post-necrotic liver fibrosis in massive and submassive hepatic necrosis. Virchows Arch. 1995; 426: 95-101.
73. 73 Olaso E, Santisteban A, Bidaurrazaga J, Gressner AM, Rosenbaum J, Vidal-Vanaclocha F. Tumor-dependent activation of rodent hepatic stellate cells during experimental melanoma metastasis. Hepatology 1997; 26: 634-42.
74. 74 Kawada N, Uoya M, Seki S, Kuroki T, Kobayashi K. Regulation by cAMP of STAT1 activation in hepatic stellate cells. Biochem. Biophys. Res. Commun. 1997; 233: 464-9.
75. 75 Koritschoner NP, Bocco JL, Panzetta-Dutari GM, Dumur CI, Flury A, Patrito LC. A novel human zinc finger protein that interacts with the core promoter element of a TATA box-less gene. J. Biol. Chem. 1997; 272: 9573-80.
76. 76 Ratziu V, Lalazar A, Wong L et al. Zf9, a Kruppel-like transcription factor upregulated in vivo during early hepatic fibrosis. Proc. Natl Acad. Sci. USA 1998; 95: 9500-5.
77. 77 Ratziu R, Kim SJ, Kim YS, Dang S, Wong L, Friedman SL. A key role for Zf9 in hepatic fibrosis via its transcriptional activation of TGFβ1 and types I and II TGFβ receptors genes in rat stellate cells. Hepatology 1997; 26: 185A.
78. 78 Kim Y, Ratziu V, Choi SG et al. Transcriptional activation of transforming growth factor beta 1 and its receptors by the Kruppel-like factor Zf9/core promoter-binding protein and Sp1. Potential mechanisms for autocrine fibrogenesis in response to injury. J. Biol. Chem. 1998; 273: 33 750-8.
79. 79 Friedman SL, Hayashi S, Suzuki Y, Kojima S. Zf9, a novel transcriptional regulator of urokinase-type plasminogen activator in endothelial cells: Implications for hepatic and vascular injury. Hepatology 1998; 28: 440A.
80. 80 Hellerbrand C, Jobin C, Iimuro Y, Licato L, Sartor RB, Brenner DA. Inhibition of NFkappaB in activated rat hepatic stellate cells by proteasome inhibitors and an IkappaB super-repressor (see comments). Hepatology 1998; 27: 1285-95.
81. 81 Taub R. Blocking NF-kappaB in the liver: The good and bad news (editorial; comment). Hepatology 1998; 27: 1445-6.
82. 82 Friedman SL. Hepatic stellate cells. Prog. Liver Dis. 1996; 14: 101-30.
83. 83 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: 1563-9.
84. 84 Pinzani M, Milani S, Grappone C, Weber FJ, Gentilini P, Abboud HE. Expression of platelet-derived growth factor in a model of acute liver injury. Hepatology 1994; 19: 701-7.
85. 85 Marshall CJ. Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell 1995; 80: 179-85.
86. 86 Marshall CJ. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr. Opin. Genet. Dev. 1994; 4: 82-9.
87. 87 Marra F, Gentilini A, Pinzani M et al. Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells (see comments). Gastroenterology 1997; 112: 1297-306.
88. 88 Failli P, Ruocco C, De FR et al. The mitogenic effect of platelet-derived growth factor in human hepatic stellate cells requires calcium influx. Am. J. Physiol. 1995; 265: C1133-9.
89. 2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts. Am. J. Physiol. 1993; 265: C1239-46.
90. 90 Di Sario A, Baroni GS, Bendia E et al. Characterization of ion transport mechanisms regulating intracellular pH in hepatic stellate cells. Am. J. Physiol. 1997; 273: G39-48.
91. 91 Rockey DC, Fouassier L, Chung JJ et al. Cellular localization of endothelin-1 and increased production in liver injury in the rat: Potential for autocrine and paracrine effects on stellate cells. Hepatology 1998; 27: 472-80.
92. 92 Pinzani M, Milani S, De FR et al. Endothelin 1 is over-expressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 1996; 110: 534-48.
93. 93 Marra F, Grandaliano G, Valente AJ, Abboud HE. Thrombin stimulates proliferation of liver fat-storing cells and expression of monocyte chemotactic protein-1: Potential role in liver injury. Hepatology 1995; 22: 780-7.
94. 94 Rosenbaum J, Blazejewski S, Preaux AM, Mallat A, Dhumeaux D, Mavier P. Fibroblast growth factor 2 and transforming growth factor beta 1 interactions in human liver myofibroblasts. Gastroenterology 1995; 109: 1986-96.
95. 95 Skrtic S, Wallenius V, Ekberg S, Brenzel A, Gressner AM, Jansson JO. Insulin-like growth factors stimulate expression of hepatocyte growth factor but not transforming growth factor beta1 in cultured hepatic stellate cells. Endocrinology 1997; 138: 4683-9.
96. 96 Pinzani M, Abboud HE, Aron DC. Secretion of insulin-like growth factor-I and binding proteins by rat liver fat-storing cells: Regulatory role of platelet-derived growth factor. Endocrinology 1990; 127: 2343-9.
97. 97 Reinehr RM, Kubitz R, Peters-Regehr T, Bode JG, Haussinger D. Activation of rat hepatic stellate cells in culture is associated with increased sensitivity to endothelin 1. Hepatology 1998; 28: 1566-77.
98. 98 Rockey DC. The cellular pathogenesis of portal hypertension: Stellate cell contractility, endothelin, and nitric oxide. Hepatology 1997; 25: 2-5.
99. 99 Kawada N, Kuroki T, Kobayashi K, Inoue M, Kaneda K, Decker K. Action of endothelins on hepatic stellate cells. J. Gastroenterol. 1995; 30: 731-8.
100. 100 Rockey DC, Weisiger RA. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: Implications for regulation of portal pressure and resistance. Hepatology 1996; 24: 233-40.
101. 101 Bauer M, Paquette NC, Zhang JX et al. Chronic ethanol consumption increases hepatic sinusoidal contractile response to endothelin-1 in the rat. Hepatology 1995; 22: 1565-76.
102. 102 Bataller R, Nicolas JM, Gines P et al. Arginine vasopressin induces contraction and stimulates growth of cultured human hepatic stellate cells. Gastroenterology 1997; 113: 615-24.
103. 103 Kawada N, Klein H, Decker K. Eicosanoid-mediated contractility of hepatic stellate cells. Biochem. J. 1992; 285: 367-71.
104. 104 Kawada N, Inoue M. Effect of adrenomedullin on hepatic pericytes (stellate cells) of the rat. FEBS Lett. 1994; 356: 109-13.
105. 105 Rockey DC, Chung JJ. Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. J. Clin. Invest. 1995; 95: 1199-206.
106. 106 Gupta TK, Toruner M, Groszmann RJ. Intrahepatic modulation of portal pressure and its role in portal hypertension. Role of nitric oxide. Digestion 1998; 59: 413-15.
107. 107 Groszmann RJ. Nitric oxide and hemodynamic impairment. Digestion 1998; 59 (Suppl. 2): 6-7.
108. 108 Rockey DC, Boyles JK, Gabbiani G, Friedman SL. Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture. J. Submicrosc. Cytol. Pathol. 1992; 24: 193-203.
109. 109 Pietrangelo A. Metals, oxidative stress and hepatic fibrogenesis. Semin. Liver Dis. 1996; 16: 13-30.
110. 110 Castilla A, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy (see comments). N. Engl. J. Med. 1991; 324: 933-40.
111. 111 Bissell DM, Wang SS, Jarnagin WR, Roll FJ. Cell-specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine regulation of hepatocyte proliferation. J. Clin. Invest. 1995; 96: 447-55.
112. 112 Ji C, Casinghino S, McCarthy TL, Centrella M. Multiple and essential Sp1 binding sites in the promoter for transforming growth factor-beta type 1 receptor. J. Biol. Chem. 1997; 272: 21 260-7.
113. 113 Friedman SL, Yamasaki G, Wong L. Modulation of transforming growth factor beta receptors of rat lipocytes during the hepatic wound healing response. Enhanced binding and reduced gene expression accompany cellular activation in culture and in vivo. J. Biol. Chem. 1994; 269: 10 551-8.
114. 114 Marra F, Romanelli RG, Pastacaldi S et al. Monocyte chemotactic protein-1 stimulates hepatic stellate cell migration. J. Hepatol. 1998; 28 (Suppl. 1): 57.
115. 115 Okuno M, Sato T, Kitamoto T et al. Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis: A potential link between retinoid loss and TGF-β mediated fibrogenesis via RARa activation. J. Hepatol. 1999; (in press).
116. 116 Ohata M, Lin M, Satre M, Tsukamoto H. Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver fibrosis. Am. J. Physiol. 1997; 272: G589-96.
117. 117 Marra F, DeFranco R, Grappone C et al. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: Correlation with monocyte infiltration. Am. J. Pathol. 1998; 152: 423-30.
118. 118 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: 1674-80.
119. 119 Maher JJ, Lozier JS, Scott MK. Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo. Am. J. Physiol. 1998; 275: G847-53.
120. 120 Marra F, Pastacaldi S, Romanelli RG et al. Integrin-mediated stimulation of monocyte chemotactic protein-1 expression. FEBS Lett. 1997; 414: 221-5.
121. 121 Sprenger H, Kaufmann A, Garn H, Lahme B, Gemsa D, Gressner AM. Induction of neutrophil-attracting chemokines in transforming rat hepatic stellate cells. Gastroenterology 1997; 113: 277-85.
122. 122 Wang SC, Tsukamoto H, Rippe RA, Schrum L, Ohata M. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J. Biol. Chem. 1998; 273: 302-8.
123. 123 Thompson KC, Trowern A, Fowell A et al. Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation in vitro. Hepatology 1998; 28: 1518-24.
124. 124 van Hogezand RA, Verspaget HW. New therapies for inflammatory bowel disease: An update on chimeric anti-TNF alpha antibodies and IL-10 therapy. Scand. J. Gastroenterol. 1997; 223 (Suppl.): 105-7.
125. 125 Thompson K, Maltby J, Fallowfield J, McAulay M, Millward-Sadler H, Sheron N. Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology 1998; 28: 1597-606.
126. 126 Louis H, Van Laethem JL, Wu W et al. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 1998; 28: 1607-15.
127. 127 Tsukamoto H. Is interleukin-10 antifibrogenic in chronic liver injury? Hepatology 1998; 28: 1707-9.
128. 128 Ashkenazi A, Dixit VM. Death receptors: Signaling and modulation. Science 1998; 281: 1305-8.
129. 129 Evan G, Littlewood T. A matter of life and cell death. Science 1998; 281: 1317-22.
130. 130 Thornberry NA, Lazebnik Y. Caspases: Enemies within. Science 1998; 281: 1312-16.
131. 131 Adams JM, Cory S. The Bcl-2 protein family: Arbiters of cell survival. Science 1998; 281: 1322-6.
132. 132 Gong W, Pecci A, Roth S, Lahme B, Beato M, Gressner AM. Transformation-dependent susceptibility of rat hepatic stellate cells to apoptosis induced by soluble Fas ligand. Hepatology 1998; 28: 492-502.
133. 133 Desmouliere A, Badid C, Bochaton-Piallat ML, Gabbiani G. Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury. Int. J. Biochem. Cell. Biol. 1997; 29: 19-30.
134. 134 Sugiyama H, Kashihara N, Maeshima Y et al. Regulation of survival and death of mesangial cells by extracellular matrix. Kidney Int. 1998; 54: 1188-96.
135. 135 Shi YB, Li Q, Damjanovski S, Amano T, Ishizuya-Oka A. Regulation of apoptosis during development: Input from the extracellular matrix. Int. J. Mol. Med. 1998; 2: 273-82.
136. 136 McHutchison JG, Gordon SC, Schiff ER et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. International Hepatitis Interventional Therapy Group. N. Engl. J. Med. 1998; 339: 1485-92.
137. 137 Davis GL, Esteban-Mur R, Rustgi V et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. N. Engl. J. Med. 1998; 339: 1493-9.
138. 138 Lai CL, Chien RN, Leung NW et al. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N. Engl. J. Med. 1998; 339: 61-8.
139. 139 Kirk AP, Jain S, Pocock S, Thomas HC, Sherlock S. Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis. Gut 1980; 21: 78-83.
140. 2 delays collagen formation in nutritional injury in rat liver. Hepatology 1988; 8: 61-4.
141. 1 analog reduces rat hepatic and Ito cell collagen gene expression and collagen accumulation after bile duct ligation injury. Hepatology 1993; 17: 707-14.
142. 142 Beno DW, Rapp UR, Davis BH. Prostaglandin E suppression of platelet-derived-growth-factor-induced Ito cell mitogenesis occurs independent of raf perinuclear translocation and nuclear proto-oncogene expression. Biochim. Biophys. Acta 1994; 1222: 292-300.
143. 143 Bodenheimer Jr H, Schaffner F, Pezzullo J. Evaluation of colchicine therapy in primary biliary cirrhosis. Gastroenterology 1988; 95: 124-9.
144. 144 Kaplan MM, Alling DW, Zimmerman HJ et al. A prospective trial of colchicine for primary biliary cirrhosis. N. Engl. J. Med. 1986; 315: 1448-54.
145. 145 Kershenobich D, Vargas F, Garcia-Tsao G, Perez Tamayo R, Gent M, Rojkind M. Colchicine in the treatment of cirrhosis of the liver. N. Engl. J. Med. 1988; 318: 1709-13.
146. 146 Rodriguez L, Cerbon-Ambriz J, Munoz ML. Effects of colchicine and colchiceine in a biochemical model of liver injury and fibrosis. Arch. Med. Res. 1998; 29: 109-16.
147. 147 Ala-Kokko L, Stenback F, Ryhanen L. Preventive effect of malotilate on carbon tetrachloride-induced liver damage and collagen accumulation in the rat. Biochem. J. 1987; 246: 503-9.
148. 148 Ala-Kokko L, Stenback F, Ryhanen L. Preventive effect of malotilate on dimethylnitrosamine-induced liver fibrosis in the rat. J. Lab. Clin. Med. 1989; 113: 177-83.
149. 149 Ryhanen L, Stenback F, Ala-Kokko L, Savolainen ER. The effect of malotilate on type III and type IV collagen, larninin and fibronectin metabolism in dimethylnitrosamine-induced liver fibrosis in the rat. J. Hepatol. 1996; 24: 238-45.
150. 150 Kim SG, Kwak JY, Lee JW, Novak RF, Park SS, Kim ND. Malotilate, a hepatoprotectant, suppresses CYP2E1 expression in rats. Biochem. Biophys. Res. Commun. 1994; 200: 1414-20.
151. 151 van Buuren HR. The results of a randomized double blind controlled trial evaluating malotilate in primary biliary cirrhosis. A European multicentre study group. J. Hepatol. 1993; 17: 227-35.
152. 152 Keiding S, Badsberg JH, Becker U et al. The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival. J. Hepatol. 1994; 20: 454-60.
153. 153 Poupon RE, Lindor KD, Cauch-Dudek K, Dickson ER, Poupon R, Heathcote EJ. Combined analysis of randomized controlled trials of ursodeoxycholic acid in primary biliary cirrhosis. Gastroenterology 1997; 113: 884-90.
154. 154 Nakamura K, Yoneda M, Yokohama S et al. Efficacy of ursodeoxycholic acid in Japanese patients with type 1 autoimmune hepatitis. J. Gastroenterol. Hepatol. 1998; 13: 490-5.
155. 155 Poo JL, Feldmann G, Erlinger S et al. Ursodeoxycholic acid limits liver histologic alterations and portal hypertension induced by bile duct ligation in the rat. Gastroenterology 1992; 102: 1752-9.
156. 156 Tanaka K, Honda M, Kuramochi T, Morioka S. Prominent inhibitory effects of transilast on migration and proliferation of and collagen synthesis by vascular smooth muscle cells. Atherosclerosis 1994; 107: 179-85.
157. 157 Ikeda H, Inao M, Fujiwara K. Inhibitory effect of transilast on activation and transforming growth factor beta 1 expression in cultured rat stellate cells. Biochem. Biophys. Res. Commun. 1996; 227: 322-7.
158. 158 Mancini R, Benedetti A, Jezequel AM. An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver. Virchows Arch. 1994; 424: 25-31.
159. 159 Fort J, Oberti F, Pilette C et al. Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats. Hepatology 1998; 28: 1525-31.
160. 160 Karalis K, Mastorakos G, Chrousos GP, Tolis G. Somatostatin analogues suppress the inflammatory reaction in vivo. J. Clin. Invest. 1994; 93: 2000-6.
161. 161 Wynn TA, Cheever AW, Jankovic D et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 1995; 376: 594-6.
162. 162 Sher A, Jankovic D, Cheever A, Wynn T. An IL-12-based vaccine approach for preventing immunopathology in schistosomiasis. Ann. NY Acad. Sci. 1996; 795: 202-7.
163. 163 Sugawara H, Ueno T, Torimura T, Inuzuka S, Tanikawa K. Inhibitory effect of OPC-15161, a component of fungus Thielavia minor, on proliferation and extracellular matrix production of rat cultured hepatic stellate cells. J. Cell Physiol. 1998; 174: 398-406.
164. 164 Sanaka T, Nakano Y, Nishimura H et al. Therapeutic effect of a newly developed antioxidative agent (OPC-15161) on experimental immune complex nephritis. Nephron 1997; 76: 315-22.
165. 1 in vitro. Curr. Eye Res. 1998; 17: 933-40.
166. 166 Muriel P. Alpha-interferon prevents liver collagen deposition and damage induced by prolonged bile duct obstruction in the rat. J. Hepatol. 1996; 24: 614-21.
167. 167 Fort J, Pilette C, Veal N et al. Effects of long-term administration of interferon alpha in two models of liver fibrosis in rats. J. Hepatol. 1998; 29: 263-70.
168. 168 Manabe N, Chevallier M, Chossegros P et al. Interferon-alpha 2b therapy reduces liver fibrosis in chronic non-A, non-B hepatitis: A quantitative histological evaluation. Hepatology 1993; 18: 1344-9.
169. 169 Poynard T, McHutchinson J, Davis G et al. Impact of interferon alfa-2b and ribavirin on the liver fibrosis progression in patients with chronic hepatitis C. Hepatology 1998; 28: 497A.
170. 170 Rockey DC, Maher JJ, Jarnagin WR, Gabbiani G, Friedman SL. Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. Hepatology 1992; 16: 776-84.
171. 171 Rockey DC, Chung JJ. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: Implications for treatment of hepatic fibrosis. J. Invest. Med. 1994; 42: 660-70.
172. 172 Toyonaga T, Hino O, Sugai S et al. Chronic active hepatitis in transgenic mice expressing interferon-gamma in the liver. Proc. Natl Acad. Sci. USA 1994; 91: 614-18.
173. 173 Pietrangelo A, Gualdi R, Casalgrandi G, Montosi G, Ventura E. Molecular and cellular aspects of iron-induced hepatic cirrhosis in rodents. J. Clin. Invest. 1995; 95: 1824-31.
174. 174 Brown KE, Poulos JE, Li L et al. Effect of vitamin E supplementation on hepatic fibrogenesis in chronic dietary iron overload. Am. J. Physiol. 1997; 272: G116-23.
175. 175 Kawada N, Seki S, Inoue M, Kuroki T. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells. Hepatology 1998; 27: 1265-74.
176. 176 Ferenci P, Dragosics B, Dittrich H et al. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J. Hepatol. 1989; 9: 105-10.
177. 177 Geerts A, Rogiers V. Sho-saiko-to: The right blend of traditional Oriental medicine and liver cell biology. Hepatology 1999; 29: 282-4.
178. 178 Boigk G, Stroedter L, Herbst H, Waldschmidt J, Riecken EO, Schuppan D. Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats. Hepatology 1997; 26: 643-9.
179. 170 Dehmlow C, Erhard J, de Groot H. Inhibition of Kupffer cell functions as an explanation for the hepatoprotective properties of silibinin. Hepatology 1996; 23: 749-54.
180. 180 Pietrangelo A, Borella F, Casalgrandi G et al. Antioxidant activity of silybin in vivo during long-term iron overload in rats. Gastroenterology 1995; 109: 1941-9.
181. 181 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. USA 1999; 96: 2345-9.
182. 182 Tsang ML, Zhou L, Zheng BL et al. Characterization of recombinant soluble human transforming growth factor-beta receptor type II (rhTGF-beta sRII). Cytokine 1995; 7: 389-97.
183. 183 George J, Roulot D, Koteliansky VE, Bissell MD. Inhibition of rat hepatic fibrogenesis by a soluble TGF beta type II receptor. Hepatology 1998; 28: 312A.
184. 184 Spearman M, Taylor WR, Greenberg AH, Wright JA. Antisense oligodeoxyribonucleotide inhibition of TGF-beta 1 gene expression and alterations in the growth and malignant properties of mouse fibrosarcoma cells. Gene 1994; 149: 25-9.
185. 185 Border WA, Noble NA, Yamamoto T et al. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature 1992; 360: 361-4.
186. 186 Roth S, Michel K, Gressner AM. (Latent) transforming growth factor beta in liver parenchymal cells, its injury-dependent release, and paracrine effects on rat hepatic stellate cells. Hepatology 1998; 27: 1003-12.
187. 187 Luscher TF, Wenzel RR. Endothelin and endothelin antagonists: Pharmacology and clinical implications. Agents Actions 1995; 45 (Suppl.): 237-53.
188. 188 Rockey DC, Chung JJ. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J. Clin. Invest. 1996; 98: 1381-8.
189. 189 Matsuda Y, Matsumoto K, Yamada A et al. Preventive and therapeutic effects in rats of hepatocyte growth factor infusion on liver fibrosis/cirrhosis. Hepatology 1997; 26: 81-9.
190. 190 Kaido T, Yoshikawa A, Seto S et al. Portal branch ligation with a continuous hepatocyte growth factor supply makes extensive hepatectomy possible in cirrhotic rats. Hepatology 1998; 28: 756-60.
191. 191 Ueki T, Kaneda Y, Tsutsui H et al. Hepatocyte growth factor gene therapy of liver cirrhosis in rats. Nat. Med. 1999; 5: 226-30.
192. 192 Yasuda H, Imai E, Shiota A, Fujise N, Morinaga T, Higashio K. Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats. Hepatology 1996; 24: 636-42.
193. 193 Masunaga H, Fujise N, Shiota A et al. Preventive effects of the deleted form of hepatocyte growth factor against various liver injuries. Eur. J. Pharmacol. 1998; 342: 267-79.
194. 194 Unemori EN, Pickford LB, Salles AL et al. Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo. J. Clin. Invest. 1996; 98: 2739-45.
195. 195 Franklin TJ. Therapeutic approaches to organ fibrosis. Int. J. Biochem. Cell Biol. 1997; 29: 79-89.
196. 196 Beno DW, Awad JA, Davis BH. Gamma-linolenic acid suppression of hepatic Ito cell mitogenesis: Post-PDGF receptor prostaglandin-independent mechanism. Am. J. Physiol. 1993; 265: C1388-95.
197. 197 Beno DW, Mullen J, Davis BH. Lipoxygenase inhibitors block PDGF-induced mitogenesis: A MAPK-independent mechanism that blocks fos and egr. Am. J. Physiol. 1995; 268: C604-10.
198. 198 Mallat A, Preaux AM, Blazejewski S, Dhumeaux D, Rosenbaum J, Mavier P. Effect of simvastatin, an inhibitor of hydroxy-methylglutaryl coenzyme A reductase, on the growth of human Ito cells. Hepatology 1994; 20: 1589-94.
199. 199 Pinzani M, Marra F, Caligiuri A et al. Inhibition by pentoxifylline of extracellular signal-regulated kinase activation by platelet-derived growth factor in hepatic stellate cells. Br. J. Pharmacol. 1996; 119: 1117-24.
200. 200 Preaux AM, Mallat A, Rosenbaum J, Zafrani ES, Mavier P. Pentoxifylline inhibits growth and collagen synthesis of cultured human hepatic myofibroblast-like cells. Hepatology 1997; 26: 315-22.
201. 201 Isbrucker RA, Peterson TC. Platelet-derived growth factor and pentoxifylline modulation of collagen synthesis in myofibroblasts. Toxicol. Appl. Pharmacol. 1998; 149: 120-6.
202. 202 Houglum K, Lee KS, Chojkier M. Proliferation of hepatic stellate cells is inhibited by phosphorylation of CREB on serine 133. J. Clin. Invest. 1997; 99: 1322-8.
203. 203 Lieber CS, Robins SJ, Li J et al. Phosphatidylcholine protects against fibrosis and cirrhosis in the baboon (see comments). Gastroenterology 1994; 106: 152-9.
204. 204 Brady LM, Fox ES, Fimmel CJ. Polyenylphosphatidylcholine inhibits PDGF-induced proliferation in rat hepatic stellate cells. Biochem. Biophys. Res. Commun. 1998; 248: 174-9.
205. 205 Sakaida I, Matsumura Y, Kubota M, Kayano K, Takenaka K, Okita K. The prolyl 4-hydroxylase inhibitor HOE 077 prevents activation of Ito cells, reducing procollagen gene expression in rat liver fibrosis induced by choline-deficient L-amino acid-defined diet. Hepatology 1996; 23: 755-63.
206. 206 Wang YJ, Wang SS, Bickel M, Guenzler V, Gerl M, Bissell DM. Two novel antifibrotics, HOE 077 and Safironil, modulate stellate cell activation in rat liver injury: Differential effects in males and females. Am. J. Pathol. 1998; 152: 279-87.
207. 207 Bissell DM. Sex and hepatic fibrosis. Hepatology 1999; 29: 988-9.
208. 208 Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR and DOSVIRC Groups. Lancet 1997; 349: 825-32.
209. 209 Nagler A, Katz A, Aingorn H et al. Inhibition of glomerular mesangial cell proliferation and extracellular matrix deposition by halofuginone. Kidney Int. 1997; 52: 1561-9.
210. 210 Pines M, Knopov V, Genina O, Lavelin I, Nagler A. Halofuginone, a specific inhibitor of collagen type I synthesis, prevents dimethylnitrosamine-induced liver cirrhosis. J. Hepatol. 1997; 27: 391-8.
211. 211 Halevy O, Nagler A, Levi-Schaffer F, Genina O, Pines M. Inhibition of collagen type I synthesis by skin fibroblasts of graft versus host disease and scleroderma patients: Effect of halofuginone. Biochem. Pharmacol. 1996; 52: 1057-63.
212. 212 Nagler A, Firman N, Feferman R, Cotev S, Pines M, Shoshan S. Reduction in pulmonary fibrosis in vivo by halofuginone. Am. J. Respir. Crit. Care Med. 1996; 154: 1082-6.
213. 213 Pines M, Nagler A. Halofuginone: A novel antifibrotic therapy. Gen. Pharmacol. 1998; 30: 445-50.
214. 214 Sakaida I, Matsumura Y, Akiyama S, Hayashi K, Ishige A, Okita K. Herbal medicine Sho-saiko-to (TJ-9) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet. J. Hepatol. 1998; 28: 298-306.
215. 215 Miyamura M, Ono M, Kyotani S, Nishioka Y. Effects of sho-saiko-to extract on fibrosis and regeneration of the liver in rats. J. Pharm. Pharmacol. 1998; 50: 97-105.
216. 216 Shimizu I, Ma YR, Mizobuchi Y et al. Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats. Hepatology 1999; 29: 149-60.
217. 217 Wasser S, Ho JM, Ang HK, Tan CE. Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats. J. Hepatol. 1998; 29: 760-71.
218. 218 Arthur MJ, Mann DA, Iredale JP. Tissue inhibitors of metalloproteinases, hepatic stellate cells and liver fibrosis. J. Gastroenterol. Hepatol. 1998; 13 (Suppl.): S33-8.
219. 219 Arthur MJ. Pathogenesis, experimental manipulation and treatment of liver fibrosis. Exp. Nephrol. 1995; 3: 90-5.
220. 220 Gressner AM. The cell biology of liver fibrogenesis: An imbalance of proliferation, growth arrest and apoptosis of myofibroblasts. Cell Tissue Res. 1998; 292: 447-52.