Molecular Mechanism of Stellate Cell Activation and Extracellular Matrix Remodeling

Extracellular Matrix and The Liver: Approach to Gene Therapy

Volumn , Issue , 2003, Pages 155-178

  Li, Dan ^a   Friedman, Scott L ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 78649884101     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-012525251-5/50010-5     Document Type: Chapter

References (180)

1. Andus T., Ramadori G., Heinrich P.C., Knittel T., Meyer zum Buschenfelde K.H. Cultured Ito cells of rat liver express the alpha 2-macroglobulin gene. Eur. J. Biochem. 1987, 168:641-646.
2. Ankoma-Sey V., Matli M., Chang K.B., Lalazar A., Donner D.B., Wong L., Warren R.S., Friedman S.L. Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 1998, 17:115-121.
3. Arenson D.M., Friedman S.L., Bissell D.M. Formation of extracellular matrix in normal rat liver: Lipocytes as a major source of proteoglycan. Gastroenterology 1988, 95:441-447.
4. Arthur M.J., Stanley A., Iredale J.P., Rafferty J.A., Hembry R.M., Friedman S.L. 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.
5. Arthur M.J. Collagenases and liver fibrosis. J. Hepatol. 1995, 22:43-48.
6. Arthur M.J. Fibrosis and altered matrix degradation. Digestion 1998, 59:376-380.
7. Attisano L., Wrana J.L. Mads and Smads in TGF beta signalling. Curr. Opin. Cell Biol. 1998, 10:188-194.
8. Bachem M.G., Meyer D., Melchior R., Sell K.M., Gressner A.M. Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblastlike cells: A potential mechanism of self perpetuation in liver fibrogenesis. J. Clin. Invest. 1992, 89:19-27.
9. Bedossa P., Houglum K., Trautwein C., Holstege A., Chojkier M. Stimulation of collagen alpha 1(I) gene expression is associated with lipid peroxidation in hepatocellular injury: A link to tissue fibrosis?. Hepatology 1994, 19:1262-1271.
10. Benyon R.C., Iredale J.P., Goddard S., Winwood P.J., Arthur M.J. Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver. Gastroenterology 1996, 110:821-831.
11. Bioulac-Sage P., Lafon M.E., Saric J., Balabaud C. Nerves and perisinusoidal cells in human liver. J. Hepatol. 1990, 10:105-112.
12. Bissell D.M., Wang S.S., Jarnagin W.R., Roll F.J. Cell-specific expression of transforming growth factor-beta in rat liver: Evidence for autocrine regulation of hepatocyte proliferation. J. Clin. Invest. 1995, 96:447-455.
13. Bruck R., Shirin H., Hershkoviz R., Lider O., Kenet G., Aeed H., Matas Z., Zaidel L., Halpern Z. 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, 40:133-138.
14. Carloni V., Romanelli R.G., Pinzani M., Laffi G., Gentilini P. Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells. Gastroenterology 1996, 110:1127-1136.
15. Carloni V., Romanelli R.G., 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, 112:522-531.
16. Castilla A., Prieto J., Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease: Effects of interferon alfa therapy. N. Engl. J. Med. 1991, 324:933-940.
17. Clark E.A., Brugge J.S. Integrins and signal transduction pathways: The road taken. Science 1995, 268:233-239.
18. Czaja M.J., Geerts A., Xu J., Schmiedeberg P., Ju Y. Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease. J. Leuk. Biol. 1994, 55:120-126.
19. Davis B.H. Transforming growth factor beta responsiveness is modulated by the extracellular collagen matrix during hepatic ito cell culture. J. Cell Physiol. 1988, 136:547-553.
20. Davis B.H., Kramer R.T., Davidson N.O. Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production. J. Clin. Invest. 1990, 86:2062-2070.
21. de Bleser P.J., Jannes P., van Buul-Offers S.C., Hoogerbrugge C.M., van Schravendijk C.F., Niki T., Rogiers V., van den Brande J.L., Wisse E., Geerts A. Insulinlike growth factor-II/mannose 6-phosphate receptor is expressed on CCl4-exposed rat fat-storing cells and facilitates activation of latent transforming growth factor-beta in cocultures with sinusoidal endothelial cells. Hepatology 1995, 21:1429-1437.
22. Desmouliere A., Badid C., Bochaton-Piallat M.L., Gabbiani G. Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury. Int. J. Biochem. Cell Biol. 1997, 29:19-30.
23. Dooley S., Delvoux B., Lahme B., Mangasser-Stephan K., Gressner A.M. Modulation of transforming growth factor beta response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts. Hepatology 2000, 31:1094-1106.
24. Duncan M.R., Frazier K.S., Abramson S., Williams S., Klapper H., Huang X., Grotendorst G.R. Connective tissue growth factor mediates transforming growth factor beta-induced collagen synthesis: Down-regulation by cAMP. FASEB J. 1999, 13:1774-1786.
25. el Hag I.A., Hashim F.A., el Toum I.A., Homeida M., el Kalifa M., el Hassan A.M., Torimura T., Ueno T., Inuzuka S., Kin M., Ohira H., Kimura Y., Majima Y., Sata M., Abe H., Tanikawa K. Liver morphology and function in visceral leishmaniasis (Kala-azar). J. Clin. Pathol. 1994, 47:547-551.
26. Enzan H., Himeno H., Iwamura S., Onishi S., Saibara T., Yamamoto Y., Hara H. Alpha-smooth muscle actin-positive perisinusoidal stromal cells in human hepatocellular carcinoma. Hepatology 1994, 19:895-903.
27. Enzan H., Himeno H., Iwamura S., Saibara T., Onishi S., Yamamoto Y., Miyazaki E., Hara H. Sequential changes in human Ito cells and their relation to postnecrotic liver fibrosis in massive and submassive hepatic necrosis. Virch. Arch. 1995, 426:95-101.
28. Friedman S.L. Seminars in medicine of the Beth Israel Hospital. N. Engl. J. Med. 1993, 328:1828-1835.
29. Friedman S.L. Hepatic stellate cells. Progr. Liver Dis. 1996, 14:101-130.
30. Friedman S.L. Cytokines and fibrogenesis. Semin. Liver Dis. 1999, 19:129-140.
31. Friedman S.L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem. 2000, 275:2247-2250.
32. Friedman S.L., Roll F.J., Boyles J., Arenson D.M., Bissell D.M. Maintenance of differentiated phenotype of cultured rat hepatic lipocytes by basement membrane matrix. J. Biol. Chem. 1989, 264:10756-10762.
33. Friedman S.L., Roll F.J., Boyles J., Bissell D.M. Hepatic lipocytes: The principal collagen-producing cells of normal rat liver. Proc. Natl. Acad. Sci. USA 1985, 82:8681-8685.
34. Friedman S.L., Wei S., Blaner W.S. Retinol release by activated rat hepatic lipocytes: Regulation by Kupffer cell-conditioned medium and PDGF. Am. J. Physiol. 1993, 264:G947-G952.
35. Friedman S.L., 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, 269:10551-10558.
36. Frizell E., Liu S.L., Abraham A., Ozaki I., Eghbali M., Sage E.H., Zern M.A. Expression of SPARC in normal and fibrotic livers. Hepatology 1995, 21:847-854.
37. Fujio K., Evarts R.P., Hu Z., Marsden E.R., Thorgeirsson S.S. Expression of stem cell factor and its receptor, c-kit, during liver regeneration from putative stem cells in adult rat. Lab. Invest. 1994, 70:511-516.
38. Geerts A., Vrijsen R., Rauterberg J., Burt A., Schellinck P., Wisse E. In vitro differentiation of fat-storing cells parallels marked increase of collagen synthesis and secretion. J. Hepatol. 1989, 9:59-68.
39. Geubel A.P., De Galocsy C., Alves N., Rahier J., Dive C. Liver damage caused by therapeutic vitamin A administration: Estimate of dose-related toxicity in 41 cases. Gastroenterology 1991, 100:1701-1709.
40. Gong W., Pecci A., Roth S., Lahme B., Beato M., Gressner A.M. Transformation-dependent susceptibility of rat hepatic stellate cells to apoptosis induced by soluble Fas ligand. Hepatology 1998, 28:492-502.
41. Greenwel P., Rubin J., Schwartz M., Hertzberg E.L., Rojkind M. Liver fat-storing cell clones obtained from a CCl4 cirrhotic rat are heterogeneous with regard to proliferation, expression of extracellular matrix components, interleukin-6, and connexin 43. Lab. Invest. 1993, 69:210-216.
42. Gressner A.M. Cytokines and cellular crosstalk involved in the activation of fat-storing cells. J. Hepatol. 1995, 22:28-36.
43. Gressner A.M., Bachem M.G. Cellular sources of noncollagenous matrix proteins: Role of fat-storing cells in fibrogenesis. Semin. Liver Dis. 1990, 10:30-46.
44. Gressner A.M., Bachem M.G. Molecular mechanisms of liver fibrogenesis: A homage to the role of activated fat-storing cells. Digestion 1995, 56:335-346.
45. Gressner A.M., Haarmann R. Hyaluronic acid synthesis and secretion by rat liver fat storing cells (perisinusoidal lipocytes) in culture. Biochem. Biophys. Res. Commun. 1988, 151:222-229.
46. Grotendorst G.R. Connective tissue growth factor: A mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev. 1997, 8:171-179.
47. Hautekeete M.L., Geerts A., Seynaeve C., Lazou J.M., Kloppel G., Wisse E. Contributions of light and transmission electron microscopy to the study of the human fat-storing cell. Eur. J. Morphol. 1993, 31:72-76.
48. Heldin C.H., Miyazono K., ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997, 390:465-471.
49. Heldin P., Pertoft H., Nordlinder H., Heldin C.H., Laurent T.C. Differential expression of platelet-derived growth factor alpha and beta-receptors on fat-storing cells and endothelial cells of rat liver. Exp. Cell Res. 1991, 193:364-369.
50. Hellerbrand, Wang S.C., Tsukamoto H., Brenner D.A., Rippe R.A. Expression of intracellular adhesion molecule 1 by activated hepatic stellate cells. Hepatology 1996, 24:670-676.
51. Helyar L., Bundschuh D.S., Laskin J.D., Laskin D.L. Induction of hepatic Ito cell nitric oxide production after acute endotoxemia. Hepatology 1994, 20:1509-1515.
52. Henriksen J.H., Holst J.J., Moller S., Brinch K., Bendtsen F. Increased circulating leptin in alcoholic cirrhosis: Relation to release and disposal. Hepatology 1999, 29:1818-1824.
53. Herbst H., Wege T., Milani S., Pellegrini G., Orzechowski H.D., Bechstein W.O., Neuhaus P., Gressner A.M., Schuppan D. Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis. Am. J. Pathol. 1997, 150:1647-1659.
54. Horn T., Junge J., Christoffersen P. Early alcoholic liver injury: Activation of lipocytes in acinar zone 3 and correlation to degree of collagen formation in the Disse space. J. Hepatol. 1986, 3:333-340.
55. 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-G913.
56. Housset C., Rockey D.C., Bissell D.M. Endothelin receptors in rat liver: Lipocytes as a contractile target for endothelin 1. Proc. Natl. Acad. Sci. USA 1993, 90:9266-9270.
57. Igarashi A., Nashiro K., Kikuchi K., Sato S., Ihn H., Fujimoto M., Grotendorst G.R., Takehara K. Connective tissue growth factor gene expression in tissue sections from localized scleroderma, keloid, and other fibrotic skin disorders. J. Invest. Dermatol. 1996, 106:729-733.
58. Ikejima K., Honda H., Yoshikawa M., Hirose M., Kitamura T., Takei Y., Sato N. Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology 2001, 34:288-297.
59. 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, 250:430-437.
60. Imai S., Okuno M., Moriwaki H., Muto Y., Murakami K., Shudo K., Suzuki Y., Kojima S., Sato T., Kitamoto T., Kawada N., Yoshimura H., Onuki K., Masushige S., Friedman S.L., Kato S. 9,13-di-cis-Retinoic acid induces the production of tPA and activation of latent TGF-beta via RAR alpha in a human liver stellate cell line, LI90. FEBS Lett. 1997, 411:102-106.
61. Inuzuka S., Ueno T., Torimura T., Sata M., Abe H., Tanikawa K. Immunohistochemistry of the hepatic extracellular matrix in acute viral hepatitis. Hepatology 1990, 12:249-256.
62. Iredale J.P. Tissue inhibitors of metalloproteinases in liver fibrosis. Int. J. Biochem. Cell Biol. 1997, 29:43-54.
63. Iredale J.P., Arthur M.J. Hepatocyte-matrix interactions. Gut 1994, 35:729-732.
64. Iredale J.P., Benyon R.C., Arthur M.J., Ferris W.F., Alcolado R., Winwood P.J., Clark N., Murphy G. 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.
65. Iredale J.P., Benyon R.C., Pickering J., McCullen M., Northrop M., Pawley S., Hovell C., Arthur M.J. 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.
66. Iredale J.P., Goddard S., Murphy G., Benyon R.C., Arthur M.J. Tissue inhibitor of metalloproteinase-I and interstitial collagenase expression in autoimmune chronic active hepatitis and activated human hepatic lipocytes. Clin. Sci. (Colch.) 1995, 89:75-81.
67. Ito Y., Aten J., Bende R.J., Oemar B.S., Rabelink T.J., Weening J.J., Goldschmeding R. Expression of connective tissue growth factor in human renal fibrosis. Kidney Int. 1998, 53:853-861.
68. Iwamoto H., Sakai H., Nawata H. Inhibition of integrin signaling with Arg-Gly-Asp motifs in rat hepatic stellate cells. J. Hepatol. 1998, 29:752-759.
69. Iwamoto H., Sakai H., Tada S., Nakamuta M., Nawata H. Induction of apoptosis in rat hepatic stellate cells by disruption of integrin-mediated cell adhesion. J. Lab. Clin. Med. 1999, 134:83-89.
70. Jarnagin W.R., Rockey D.C., Koteliansky V.E., Wang S.S., Bissell D.M. 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.
71. Ji C., Casinghino S., McCarthy T.L., Centrella M. Multiple and essential Sp1 binding sites in the promoter for transforming growth factor-beta type I receptor. J. Biol. Chem. 1997, 272:21260-21267.
72. Kamimura S., Gaal K., Britton R.S., Bacon B.R., Triadafilopoulos G., Tsukamoto H. Increased 4-hydroxynonenal levels in experimental alcoholic liver disease: Association of lipid peroxidation with liver fibrogenesis. Hepatology 1992, 16:448-453.
73. Kawada N., Kuroki T., Kobayashi K., Inoue M., Kaneda K., Decker K. Action of endothelins on hepatic stellate cells. J. Gastroenterol. 1995, 30:731-738.
74. Kawada N., Tran T.T., 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 the sinusoidal tonus. Eur. J. Biochem. 1993, 213:815-823.
75. 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, 233:464-469.
76. Kawase T., Shiratori Y., Sugimoto T. Collagen production by rat liver fat-storing cells in primary culture. Exp. Cell Biol. 1986, 54:183-192.
77. Kim Y., Ratziu V., Choi S.G., Lalazar A., Theiss G., Dang Q., Kim S.J., Friedman S.L. Transcriptional activation of transforming growth factor beta1 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, 273:33750-33758.
78. Knittel T., Armbrust T., Schwogler S., Schuppan D., Ramadori G. Distribution and cellular origin of undulin in rat liver. Lab. Invest. 1992, 67:779-787.
79. Knittel T., Aurisch S., Neubauer K., Eichhorst S., Ramadori G. Cell-type-specific expression of neural cell adhesion molecule (N-CAM) in Ito cells of rat liver: Up-regulation during in vitro activation and in hepatic tissue repair. Am. J. Pathol. 1996, 149:449-462.
80. Knittel T., Dinter C., Kobold D., Neubauer K., Mehde M., Eichhorst S., Ramadori G. Expression and regulation of cell adhesion molecules by hepatic stellate cells (HSC) of rat liver: Involvement of HSC in recruitment of inflammatory cells during hepatic tissue repair. Am. J. Pathol. 1999, 154:153-167.
81. Kovalszky H., Gallai M., Armbrust T., Ramadori G. Syndecan-1 gene expression in isolated rat liver cells (hepatocytes, Kupffer cells, endothelial and Ito cells). Biochem. Biophys. Res. Commun. 1994, 204:944-949.
82. Lafon M.E., Bioulac-Sage P., Le Bail B., Saric J., Quinton A., Balabaud C. Nerves and perisinusoidal cells in human liver 1989, 230-234.
83. Lasky J.A., Ortiz L.A., Tonthat B., Hoyle G.W., Corti M., Athas G., Lungarella G., Brody A., Friedman M. Connective tissue growth factor mRNA expression is upregulated in bleomycin-induced lung fibrosis. Am. J. Physiol. 1998, 275:L365-L371.
84. Leo M.A., Lieber C.S. Hepatic fibrosis after long-term administration of ethanol and moderate vitamin A supplementation in the rat. Hepatology 1983, 3:1-11.
85. Louis H., Van Laethem J.L., Wu W., Quertinmont E., Degraef C., Van den Berg K., Demols A., Goldman M., Le Moine O., Geerts A., Deviere J. Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon tetrachloride in mice. Hepatology 1998, 28:1607-1615.
86. Maher J.J. Cell-specific expression of hepatocyte growth factor in liver: Upregulation in sinusoidal endothelial cells after carbon tetrachloride. J. Clin. Invest. 1993, 91:2244-2252.
87. Maher J.J., Friedman S.L., Roll F.J., Bissell D.M. Immunolocalization of laminin in normal rat liver and biosynthesis of laminin by hepatic lipocytes in primary culture. Gastroenterology 1988, 94:1053-1062.
88. Maher J.J., Lozier J.S., Scott M.K. Rat hepatic stellate cells produce cytokine-induced neutrophil chemoattractant in culture and in vivo. Am. J. Physiol. 1998, 275:G847-G853.
89. Maher J.J., Tzagarakis C., Gimenez A. Malondialdehyde stimulates collagen production by hepatic lipocytes only upon activation in primary culture. Alcohol Alcohol. 1994, 29:605-610.
90. Marra F., Choudhury G.G., Pinzani M., Abboud H.E. Regulation of platelet-derived growth factor secretion and gene expression in human liver fat-storing cells. Gastroenterology 1994, 107:1110-1117.
91. Marra F., DeFranco R., Grappone C., Milani S., Pastacaldi S., Pinzani M., Romanelli R.G., Laffi G., Gentilini P. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: Correlation with monocyte infiltration. Am. J. Pathol. 1998, 152:423-430.
92. Marra F., Grandaliano G., Valente A.J., Abboud H.E. Thrombin stimulates proliferation of liver fat-storing cells and expression of monocyte chemotactic protein-1: Potential role in liver injury. Hepatology 1995, 22:780-787.
93. Marra F., Gentilini A., Pinzani M., Choudhury G.G., Parola M., Herbst H., Dianzani M.U., Laffi G., Abboud H.E., Gentilini P. Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells. Gastroenterology 1997, 112:1297-1306.
94. Marra F., Valente A.J., Pinzani M., Abboud H.E. Cultured human liver fat-storing cells produce monocyte chemotactic protein-1: Regulation by proinflammatory cytokines. J. Clin. Invest. 1993, 92:1674-1680.
95. Marsden E.R., Hu Z., Fujio K., Nakatsukasa H., Thorgeirsson S.S., Evarts R.P. Expression of acidic fibroblast growth factor in regenerating liver and during hepatic differentiation. Lab. Invest. 1992, 67:427-433.
96. Marti A., Berraondo B., Martinez J.A. Leptin: Physiological actions. J. Physiol. Biochem. 1999, 55:43-49.
97. Mathew J., Hines J.E., James O.F., Burt A.D. Non-parenchymal cell responses in paracetamol (acetaminophen)-induced liver injury. J. Hepatol. 1994, 20:537-541.
98. McCullough A.J., Bugianesi E., Marchesini G., Kalhan S.C. Gender-dependent alterations in serum leptin in alcoholic cirrhosis. Gastroenterology 1998, 115:947-953.
99. Meyer D.H., Bachem M.G., Gressner A.M. Modulation of hepatic lipocyte proteoglycan synthesis and proliferation by Kupffer cell-derived transforming growth factors type beta 1 and type alpha. Biochem. Biophys. Res. Commun. 1990, 171:1122-1129.
100. Meyer D.H., Krull N., Dreher K.L., Gressner A.M. Biglycan and decorin gene expression in normal and fibrotic rat liver: Cellular localization and regulatory factors. Hepatology 1992, 16:204-216.
101. Milani S., Grappone C., Pellegrini G., Schuppan D., Herbst H., Calabro A., Casini A., Pinzani M., Surrenti C. Undulin RNA and protein expression in normal and fibrotic human liver. Hepatology 1994, 20:908-916.
102. Milani S., Herbst H., Schuppan D., Grappone C., Pellegrini G., Pinzani M., Casini A., Calabro A., Ciancio G., Stefanini F., et al. Differential expression of matrix-metalloproteinase-1 and -2 genes in normal and fibrotic human liver. Am. J. Pathol. 1994, 144:528-537.
103. Minato Y., Hasumura Y., Takeuchi J. The role of fat-storing cells in Disse space fibrogenesis in alcoholic liver disease. Hepatology 1983, 3:559-566.
104. Mizobuchi Y., Shimizu I., Yasuda M., Hori H., Shono M., Ito S. Retinyl palmitate reduces hepatic fibrosis in rats induced by dimethylnitrosamine or pig serum. J. Hepatol. 1998, 29:933-943.
105. Moncada S., Higgs A. The L-arginine-nitric oxide pathway. N. Engl. J. Med. 1993, 329:2002-2012.
106. Mullhaupt B., Feren A., Fodor E., Jones A. Liver expression of epidermal growth factor RNA. Rapid increases in immediate-early phase of liver regeneration. J. Biol. Chem. 1994, 269:19667-19670.
107. Musso O., Rehn M., Saarela J., Theret N., Lietard J., Hintikka, Lotrian D., Campion J.P., Pihlajaniemi T., Clement B. 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.
108. Nakatani K., Seki S., Kawada N., Kobayashi K., Kaneda K. Expression of neural cell adhesion molecule (N-CAM) in perisinusoidal stellate cells of the human liver. Cell Tissue Res. 1996, 283:159-165.
109. 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-G596.
110. Okuno M., Moriwaki H., Imai S., Muto Y., Kawada N., Suzuki Y., Kojima S. Retinoids exacerbate rat liver fibrosis by inducing the activation of latent TGF-beta in liver stellate cells. Hepatology 1997, 26:913-921.
111. Okuno M., Sato T., Kitamoto T., Imai S., Kawada N., Suzuki Y., Yoshimura H., Moriwaki H., Onuki K., Masushige S., Muto Y., Friedman S.L., Kato S., Kojima S. Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis: Implication for a potential link between retinoid loss and TGF-beta mediated fibrogenesis in vivo. J. Hepatol. 1999, 30:1073-1080.
112. Olaso E., Eng F., Lin C., Yancopoulous G., Friedman S.L. The discoidin domain receptor 2 (DDR2) is induced during stellate cell activation, mediates cell growth and MMP2 expression, and is regulated by extracellular matrix. Hepatology 1999, 30:413A.
113. Paradis V., Kollinger M., Fabre M., Holstege A., Poynard T., Bedossa P. In situ detection of lipid peroxidation by-products in chronic liver diseases. Hepatology 1997, 26:135-142.
114. Paradis V., Dargere D., Vidaud M., De Gouville A.C., Huet S., Martinez V., Gauthier J.M., Ba N., Sobesky R., Ratziu V., Bedossa P. Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology 1999, 30:968-976.
115. Parola M., Pinzani M., Casini A., Albano E., Poli G., Gentilini A., Gentilini P., Dianzani M.U. Stimulation of lipid peroxidation or 4-hydroxynonenal treatment increases procollagen alpha 1 (I) gene expression in human liver fat-storing cells. Biochem. Biophys. Res. Commun. 1993, 194:1044-1050.
116. Pietrangelo A. Metals, oxidative stress, and hepatic fibrogenesis. Semin. Liver Dis. 1996, 16:13-30.
117. Pinzani M., Abboud H.E., Aron D.C. 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, 127:2343-2349.
118. Pinzani M., Abboud H.E., Gesualdo L., Abboud S.L. Regulation of macrophage colony-stimulating factor in liver fat-storing cells by peptide growth factors. Am. J. Physiol. 1992, 262:C876-C881.
119. Pinzani M., Carloni V., Marra F., Riccardi D., Laffi G., Gentilini P. Biosynthesis of platelet-activating factor and its 1O-acyl analogue by liver fat-storing cells. Gastroenterology 1994, 106:1301-1311.
120. Pinzani M., Failli P., Ruocco C., Casini A., Milani S., Baldi E., Giotti A., Gentilini P. Fat-storing cells as liver-specific pericytes: Spatial dynamics of agonist-stimulated intracellular calcium transients. J. Clin. Invest. 1992, 90:642-646.
121. Pinzani M., Gentilini A., Caligiuri A., De Franco R., Pellegrini G., Milani S., Marra F., Gentilini P. Transforming growth factor-beta 1 regulates platelet-derived growth factor receptor beta subunit in human liver fat-storing cells. Hepatology 1995, 21:232-239.
122. Pinzani M., Gesualdo L., Sabbah G.M., Abboud H.E. 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.
123. Pinzani M., Knauss T.C., Pierce G.F., Hsieh P., Kenney W., Dubyak G.R., Abboud H.E. Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells. Am. J. Physiol. 1991, 260:C485-C491.
124. Pinzani M., Marra F., Carloni V. Signal transduction in hepatic stellate cells. Liver 1998, 18:2-13.
125. Pinzani M., Milani S., De Franco R., Grappone C., Caligiuri A., Gentilini A., Tosti-Guerra C., Maggi M., Failli P., Ruocco C., Gentilini P. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 1996, 110:534-548.
126. Pinzani M., Milani S., Grappone C., Weber F.J., Gentilini P., Abboud H.E. Expression of platelet-derived growth factor in a model of acute liver injury. Hepatology 1994, 19:701-707.
127. Pinzani M., Milani S., Herbst H., DeFranco R., Grappone C., Gentilini A., Caligiuri A., Pellegrini G., Ngo D.V., Romanelli R.G., Gentilini P. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am. J. Pathol. 1996, 148:785-800.
128. Potter J.J., Womack L., Mezey E., Anania F.A. Transdifferentiation of rat hepatic stellate cells results in leptin expression. Biochem. Biophys. Res. Commun. 1998, 244:178-182.
129. Racine-Samson L., Rockey D.C., Bissell D.M. The role of alpha1beta1 integrin in wound contraction: A quantitative analysis of liver myofibroblasts in vivo and in primary culture. J. Biol. Chem. 1997, 272:30911-30917.
130. Ramadori G., Knittel T., Odenthal M., Schwogler S., Neubauer K., Meyer zum Buschenfelde K.H. Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: Regulation by cytokines. Gastroenterology 1992, 103:1313-1321.
131. Ramadori G., Schwogler S., Veit T., Rieder H., Chiquet-Ehrismann R., Mackie E.J., Meyer zum Buschenfelde K.H. Tenascin gene expression in rat liver and in rat liver cells. In vivo and in vitro studies. Virch. Arch. B Cell Pathol. Incl. Mol. Pathol. 1991, 60:145-153.
132. Reimann T., Hempel U., Krautwald S., Axmann A., Scheibe R., Seidel D., Wenzel K.W., Kawada N., Suzuki Y., Yoshimura H., Moriwaki H., Onuki K., Masushige S., Muto Y., Friedman S.L., Kato S., Kojima S. Transforming growth factor-beta1 induces activation of Ras, Raf-1, MEK and MAPK in rat hepatic stellate cells. FEBS Lett. 1997, 403:57-60.
133. Rescan P.Y., Loreal O., Hassell J.R., 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.
134. Resnick J.M., Whitley C.B., Leonard A.S., Krivit W., Snover D.C. Light and electron microscopic features of the liver in mucopolysaccharidosis. Hum. Pathol. 1994, 25:276-286.
135. Rockey D.C. Characterization of endothelin receptors mediating rat hepatic stellate cell contraction. Biochem. Biophys. Res. Commun. 1995, 207:725-731.
136. Rockey D.C. The cellular pathogenesis of portal hypertension: Stellate cell contractility, endothelin, and nitric oxide. Hepatology 1997, 25:2-5.
137. Rockey D.C., Chung J.J. Inducible nitric oxide synthase in rat hepatic lipocytes and the effect of nitric oxide on lipocyte contractility. J. Clin. Invest. 1995, 95:1199-1206.
138. Rockey D.C., Fouassier L., Chung J.J., Carayon A., Vallee P., Rey C., Housset C. 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, 27:472-480.
139. Rockey D.C., Housset C.N., Friedman S.L. Activation-dependent contractility of rat hepatic lipocytes in culture and in vivo. J. Clin. Invest. 1993, 92:1795-1804.
140. Rockey D.C., Weisiger R.A. Endothelin induced contractility of stellate cells from normal and cirrhotic rat liver: Implications for regulation of portal pressure and resistance. Hepatology 1996, 24:233-240.
141. Rosenbaum J., Blazejewski S., Preaux A.M., Mallat A., Dhumeaux D., Mavier P. Fibroblast growth factor 2 and transforming growth factor beta 1 interactions in human liver myofibroblasts. Gastroenterology 1995, 109:1986-1996.
142. Roskams T., Moshage H., De Vos R., Guido D., Yap P., Desmet V. Heparan sulfate proteoglycan expression in normal human liver. Hepatology 1995, 21:950-958.
143. Roulot D., Durand H., Coste T., Rautureau J., Strosberg A.D., Benarous R., Marullo S. Quantitative analysis of transforming growth factor beta 1 messenger RNA in the liver of patients with chronic hepatitis C: Absence of correlation between high levels and severity of disease. Hepatology 1995, 21:298-304.
144. Saile B., Matthes N., Knittel T., Ramadori G. Transforming growth factor beta and tumor necrosis factor alpha inhibit both apoptosis and proliferation of activated rat hepatic stellate cells. Hepatology 1999, 30:196-202.
145. Schafer S., Zerbe O., Gressner A.M. The synthesis of proteoglycans in fat-storing cells of rat liver. Hepatology 1987, 7:680-687.
146. Schirmacher P., Geerts A., Pietrangelo A., Dienes H.P., Rogler C.E. Hepatocyte growth factor/hepatopoietin A is expressed in fat-storing cells from rat liver but not myofibroblast-like cells derived from fat-storing cells. Hepatology 1992, 15:5-11.
147. Schmitt-Graff A., Chakroun G., Gabbiani G. Modulation of perisinusoidal cell cytoskeletal features during experimental hepatic fibrosis. Virch. Arch. A Pathol. Anat. Histopathol. 1993, 422:99-107.
148. Schmitt-Graff A., Kruger S., Bochard F., Gabbiani G., Denk H. Modulation of alpha smooth muscle actin and desmin expression in perisinusoidal cells of normal and diseased human livers. Am. J. Pathol. 1991, 138:1233-1242.
149. Scoazec J.Y. Expression of cell-matrix adhesion molecules in the liver and their modulation during fibrosis. J. Hepatol. 1995, 22:20-27.
150. Scoazec J.Y. Adhesion molecules in normal human liver. Hepatogastroenterology 1996, 43:1103-1105.
151. Seifert W.F., Bosma A., Brouwer A., Hendriks H.F., Roholl P.J., van Leeuwen R.E., van Thiel-de Ruiter G.C., Seifert-Bock I., Knook D.L. Vitamin A deficiency potentiates carbon tetrachloride-induced liver fibrosis in rats. Hepatology 1994, 19:193-201.
152. Seifert W.F., Bosma A., Hendriks H.F.J. Dual role of vitamin A in experimentally induced liver fibrosis 1989, 43-48.
153. Senoo H., Wake K. Suppression of experimental hepatic fibrosis by administration of vitamin A. Lab. Invest. 1985, 52:182-194.
154. Shi Y.B., Li Q., Damjanovski S., Amano T., Ishizuya-Oka A. Regulation of apoptosis during development: Input from the extracellular matrix. Int. J. Mol. Med. 1998, 2:273-282.
155. Shrivastava A., Radziejewski C., Campbell E., Kovac L., McGlynn M., Ryan T.E., Davis S., Goldfarb M.P., Glass D.J., Lemke G., Yancopoulos G.D. An orphan receptor tyrosine kinase family whose members serve as nonintegrin collagen receptors. Mol. Cell 1997, 1:25-34.
156. Sims D.E. The pericyte: A review. Tissue Cell 1986, 18:153-174.
157. Skrtic S., Wallenius V., Ekberg S., Brenzel A., Gressner A.M., Jansson J.O. Insulin-like growth factors stimulate expression of hepatocyte growth factor but not transforming growth factor beta1 in cultured hepatic stellate cells. Endocrinology 1997, 138:4683-4689.
158. Sugiyama H., Kashihara N., Maeshima Y., Okamoto K., Kanao K., Sekikawa T., Makino H. Regulation of survival and death of mesangial cells by extracellular matrix. Kidney Int. 1998, 54:1188-1196.
159. Takahara T., Furui K., Yata Y., Jin B., Zhang L.P., Nambu S., Sato H., Seiki M., Watanabe A. Dual expression of matrix metallo-proteinase-2 and membrane-type 1-matrix metalloproteinase in fibrotic human livers. Hepatology 1997, 26:1521-1529.
160. Takahara T., Sollberg S., Muona P., Uitto J. Type VI collagen gene expression in experimental liver fibrosis: Quantitation and spatial distribution of mRNAs, and immunodetection of the protein. Liver 1995, 15:78-86.
161. Theret N., Musso O., L'Helgoualc'h A., Clement B. Activation of matrix metallo-proteinase-2 from hepatic stellate cells requires interactions with hepatocytes. Am. J. Pathol. 1997, 150:51-58.
162. 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, 28:1597-1606.
163. Thompson K.C., Trowern A., Fowell A., Marathe M., Haycock C., Arthur M.J., Sheron N. Primary rat and mouse hepatic stellate cells express the macrophage inhibitor cytokine interleukin-10 during the course of activation In vitro. Hepatology 1998, 28:1518-1524.
164. Tiggelman A.M., Boers W., Linthorst C., Brand H.S., Sala M., Chamuleau R.A. Interleukin-6 production by human liver (myo)fibroblasts in culture: Evidence for a regulatory role of LPS, IL-1 beta and TNF alpha. J. Hepatol. 1995, 23:295-306.
165. Timpl R. Macromolecular organization of basement membranes. Curr. Opin. Cell Biol. 1996, 8:618-624.
166. Torimura T., Ueno T., Inuzuka S., Kin M., Ohira H., Kimura Y., Majima Y., Sata M., Abe H., Tanikawa K. The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: Immunohistochemical analysis. J. Hepatol. 1994, 21:37-46.
167. Trigueiro de Araujo M.S., Gerard F., Chossegros P., Guerret S., Barlet P., Adeleine P., Grimaud J.A., Sata M., Abe H., Tanikawa K. Cellular and matrix changes in drug abuser liver sinusoids: A semiquantitative and morphometric ultrastructural study. Virch. Arch. A Pathol. Anat. Histopathol. 1993, 422:145-152.
168. Vogel W., Gish G.D., Alves F., Pawson T. The discoidin domain receptor tyrosine kinases are activated by collagen. Mol. Cell 1997, 1:13-23.
169. Vyas S.K., Leyland H., Gentry J., Arthur M.J. Rat hepatic lipocytes synthesize and secrete transin (stromelysin) in early primary culture. Gastroenterology 1995, 109:889-898.
170. Wake K. Liver perivascular cells revealed by gold and silver impregnation methods and electron microscopy 1988, 23-36.
171. Wake K., Kishiye T., Yamamoto H., Kaneda K., Sato C. Sinusoidal cell function life under the microscope 1992, 45-51.
172. Wang S.C., Tsukamoto H., Rippe R.A., Schrum L., Ohata M. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J. Biol. Chem. 1998, 273:302-308.
173. Win K.M., Charlotte F., Mallat A., Cherqui D., Martin N., Mavier P., Preaux A.M., Dhumeaux D., Rosenbaum J. Mitogenic effect of transforming growth factor-beta 1 on human Ito cells in culture: Evidence for mediation by endogenous platelet-derived growth factor. Hepatology 1993, 18:137-145.
174. Winwood P.J., Schuppan D., Iredale J.P., Kawser C.A., Docherty A.J., Arthur M.J. Kupffer cell-derived 95-kd type IV collagenase/gelatinase B: Characterization and expression in cultured cells. Hepatology 1995, 22:304-315.
175. Wong L., Yamasaki G., Johnson R.J., Friedman S.L. 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.
176. Wrana J.L., Attisano L. MAD-related proteins in TGF-beta signalling. Trends Genet. 1996, 12:493-496.
177. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T., Duncan M.R., Frazier K.S., Abramson S., Williams S., Klapper H., Huang X., Grotendorst G.R. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332:411-415.
178. Zhang J.X., Bauer M., Clemens M.G. Vessel- and target cell-specific actions of endothelin-1 and endothelin-3 in rat liver. Am. J. Physiol. 1995, 269:G269-G277.
179. Zhang J.X., Pegoli W., Clemens M.G. Endothelin-1 induces direct constriction of hepatic sinusoids. Am. J. Physiol. 1994, 266:G624-G632.
180. Zindy F., Lamas E., Schmidt S., Kirn A., Brechot C. Expression of insulin-like growth factor II (IGF-II) and IGF-II, IGF-I and insulin receptors mRNAs in isolated non-parenchymal rat liver cells. J. Hepatol. 1992, 14:30-34.