Cytokine Receptors and Signaling in Hepatic Stellate Cells

Massimo Pinzani; Fabio Marra

doi:10.1055/s-2001-17554

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2001; 21(3): 397-416
DOI: 10.1055/s-2001-17554

Cytokine Receptors and Signaling in Hepatic Stellate Cells

Massimo Pinzani, Fabio Marra

Dipartimento di Medicina Interna, Università degli Studi di Firenze, Firenze, Italy

Abstract

ABSTRACT

Following acute or chronic liver tissue damage, hepatic stellate cells (HSCs) undergo a process of activation toward a phenotype characterized by increased proliferation, motility, contractility, and synthesis of extracellular matrix components. Activation of HSCs is regulated by several soluble factors, including growth factors, cytokines, chemokines, and products of oxidative stress, as well as by extensive changes in the composition and organization of the ECM. Different groups of soluble factors may be classified according to their prevalent biological effect: (a) factors promoting HSC proliferation and/or migration (i.e., platelet-derived growth factor, basic fibroblast growth factor, insulin-like growth factor-1); (b) factors promoting fibrillar ECM accumulation, particularly transforming growth factor-β1; (c) factors with a prevalent contractile effect on HSCs, such as endothelin-1, thrombin, angiotensin-II and vasopressin, although all these agents also may promote HSC proliferation; (d) proinflammatory cytokines and chemokines; and (e) cytokines with a prominent antiinflammatory/antifibrogenic activity, such as interleukin-10 and interferon-γ. Additional important issues are represented by the relationship between cytokine and integrin signaling, and by the effects of oxidative stress-related molecules on cytokine signaling. In the past decade the major intracellular signaling pathways elicited by these factors in HSCs have been greatly elucidated.

KEYWORD

Hepatic stellate cells - cytokine receptors - cytokine signaling - liver tissue damage

Full Text

References

REFERENCES

1 Friedman S L. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem . 2000; 275 2247-2250
2 Pinzani M. Liver fibrosis. Springer Semin Immunopathol . 2000; 21 475-490
3 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
4 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 Cell Physiol . 1992; 262 C876-C881
5 Pinzani M, Gentilini A, Caligiuri A. Transforming growth factor-w1 regulates platelet-derived growth factor subunit in human liver fat-storing cells. Hepatology . 1995; 21 232-239
6 Pinzani M, Milani S, Grappone C, Weber Jr L F, Gentilini P, Abboud H E. Expression of platelet-derived growth factor in a model of acute liver injury. Hepatology . 1994; 19 701-707
7 Pinzani M, Milani S, Herbst H. 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
8 Grappone C, Pinzani M, Parola M. Expression of platelet-derived growth factor in newly formed cholangiocytes during experimental biliary fibrosis in rats. J Hepatol . 1999; 31 100-109
9 Kinnman N, Hultcrantz R, Barbu V. PDGF-mediated chemoattraction of hepatic stellate cells by bile duct segments in cholestatic liver injury. Lab Invest . 2000; 80 697-707
10 Claesson-Welsh L. Platelet-derived receptor signals. J Biol Chem . 1994; 269 32023-32026
11 Cohen G B, Ren R, Baltimore D. Modular binding domain in signal transduction proteins. Cell . 1995; 80 237-248
12 Pawson T. Protein modules and signalling networks. Nature . 1995; 373 573-580
13 Marshall C J. Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation. Cell . 1995; 80 179-185
14 Marshall C J. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev . 1994; 4 82-89
15 Pages G, Lenormand P, L'Allemain G. Mitogen-activated protein kinases p42^MAPK and p44^MAPK are required for fibroblast proliferation. Proc Natl Acad Sci USA . 1993; 90 8319-8323
16 Marra F, Pinzani M, DeFranco R, Laffi G, Gentilini P. Involvement of phosphatidylinositol 3-kinase in the activation of extracellular signal-regulated kinase by PDGF in hepatic stellate cells. FEBS Lett . 1995; 376 141-145
17 Marra F, Ghosh Choudhury G, Abboud H E. Interferon-γ-mediated activation of STAT1α regulates growth factor-induced mitogenesis. J Clin Invest . 1996; 98 1218-1230
18 Marra F, Arrighi M C, Fazi M. ERK activation differentially regulates PDGF's actions in hepatic stellate cells, and is induced by in vivo liver injury. Hepatology . 1999; 30 951-958
19 Reeves H L, Thompson M G, Dack C L, Burt A D, Day C P. The role of phosphatidic acid in platelet-derived growth factor-induced proliferation of rat hepatic stellate cells. Hepatology . 2000; 31 95-100
20 Pinzani M, Marra F, Caligiuri A. Inhibition by pentoxifylline of extracellular signal-regulated kinase activation by platelet-derived growth factor in hepatic stellate cells. Br J Pharmacol . 1996; 119 1117-1124
21 Mallat A, Gallois C, Tao J. Platelet-derived growth factor-BB and thrombin generate positive and negative signals for human hepatic stellate cell proliferation. Role of a prostaglandin/cyclic AMP pathway and cross-talk with endothelin receptors. J Biol Chem . 1998; 273 27300-27305
22 Failli P, DeFranco R MS, Caligiuri A. Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation and migration of activated human hepatic stellate cells. Gastroenterology . 2000; 119 479-492
23 Mallat A, Preaux A M, Serradeil-Le Gal C. Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. Inhibition of both extracellular signal-regulated kinase and c-Jun kinase and upregulation of endothelin B receptors. J Clin Invest . 1996; 98 2771-2778
24 Wu J, Dent P, Jelinek T. Inhibition of the EGF-activated MAP kinase signalling pathway by adenosine 3′,5′-monophosphate. Science . 1993; 262 1065-1069
25 Graves L M, Bornfelt K E, Raines E W. Protein kinase A antagonizes platelet-derived growth factor-induced signalling by mitogen-activated protein kinase in human arterial smooth muscle cells. Proc Natl Acad Sci U S A . 1993; 90 10300-10304
26 Kawada N, Uoya M, Seki S. Regulation by cAMP of STAT1 activation in hepatic stellate cells. Biochem Biophys Res Comm . 1997; 233 464-469
27 Parker P J, Waterfield M D. Phosphatidylinositol 3-kinase: a novel effector. Cell Growth Differ . 1992; 3 747-752
28 Valius M, Kazlaukas A. Phospholipase C-gamma and phosphatidylinositol 3-kinase are the downstream mediators of the PDGF receptor's mitogenic signal. Cell . 1993; 73 321-334
29 Kundra V, Escobedo J A, Kazlaukas A. Regulation of chemotaxis by platelet-derived growth factor receptor beta. Nature . 1993; 367 474-476
30 Marra F, Gentilini A, Pinzani M. Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells. Gastroenterology . 1997; 112 1297-1306
31 Gentilini A, Marra F, Gentilini P, Pinzani M. Phosphatidylinositol-3 kinase and extracellular signal-regulated kinase mediate the chemotactic and mitogenic effects of insulin-like growth factor-I in human hepatic stellate cells. J Hepatol . 2000; 32 227-234
32 Bornfelt K E, Raines E W, Nakano T, Graves L M, Krebs E G, Ross R. Insulin-like growth factor I and platelet-derived growth factor-BB induce directed migration of human arterial smooth muscle cells via signaling pathways that are distinct from those of proliferation. J Clin Invest . 1994; 93 1266-1274
33 Issa R, Williams E, Trim N. Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut . 2001; 48 548-557
34 Datta S R, Brunet A, Greenberg M E. Cellular survival: a play in three Akts. Genes Dev . 1999; 13 2905-2927
35 Gentilini A, Romanelli R G, Marra F, Gentilini P, Pinzani M. IGF-I is a survival factor for human hepatic stellate cells (HSC): involvement of PI 3-K and c-Akt [Abstract]. J Hepatol . 2001; 34(suppl 1) 7
36 Jones S M, Kazlaukas A. Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nature Cell Biol . 2001; 3 165-172
37 Jones S M, Klinghoffer R, Prestwich G D, Toker A, Kazlaukas A. PDGF induces an early and late wave of PI 3-kinase activity, and only the late wave is required for progression trough G1. Curr Biol . 1999; 9 512-521
38 Bonacchi A, Romagnani P, Romanelli R G. Signal transduction by the chemokine receptor CXCR3. Activation of Ras/ERK, Src and PI 3-K/Akt controls cell migration and proliferation in human vascular pericytes. J Biol Chem . 2001; 276 9945-9954
39 Pinzani M, Knauss T C, Pierce G F. Mitogenic signals for platelet-derived growth factor isoforms in liver fat-storing cells. Am J Physiol . 1991; 260 C485-C491
40 Kondo T, Konishi F, Inui H, Inagami T. Differing signal transduction elicited by three isoforms of platelet-derived growth factor in vascular smooth muscle cells. J Biol Chem . 1993; 268 4458-4464
41 Wang Z, Estacion M, Mordan L J. Ca²⁺ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts. Am J Physiol . 1993; 265 C1239-C1246
42 Failli P, Ruocco C, DeFranco R. The mitogenic effect of platelet-derived growth factor in human hepatic stellate cells requires calcium influx. Am J Physiol . 1995; 269 C1133-C1139
43 Ma H, Matsunaga H, Li B, Schieffer B, Marrero M B, Ling B N. Ca²⁺ channel activation by platelet-derived growth factor-induced tyrosine phosphorylation and Ras guanine triphosphate-binding proteins in rat glomerular mesangial cells. J Clin Invest . 1996; 97 2332-2341
44 Carloni V, Pinzani M, Giusti S. Tyrosine phosphorylation of focal adhesion kinase by PDGF is dependent on Ras in human hepatic stellate cells. Hepatology . 2000; 31 131-140
45 Di Sario A, Svegliati Baroni G, Bendia E. Characterization of ion transport mechanisms regulating intracellular pH in hepatic stellate cells. Am J Physiol . 1997; 273 G39-G48
46 Di Sario A, Bendia E, Svegliati Baroni G. Intracellular pathways mediating Na⁺/H⁺ exchange activation by platelet-derived growth factor in rat hepatic stellate cells. Gastroenterology . 1999; 116 1155-1166
47 Di Sario A, Svegliati Baroni G, Bendia E. Intracellular pH regulation and Na⁺/H⁺ exchange activity in human hepatic stellate cells: effects of platelet-derived growth factor, insulin-like growth factor 1 and insulin. J Hepatol . 2001; 34 378-385
48 Benedetti A, Di Sario A, Casini A. Inhibition of the Na⁺/H⁺ exchanger reduces rat hepatic stellate cell activity and liver fibrosis: an in vitro and in vivo study. Gastroenterology . 2001; 120 545-556
49 Caligiuri A, Marra F, Failli P. Cross-talk between phosphatidylinositol 3-kinase (PI3-K) and the Na⁺/H⁺ exchanger in hepatic stellate cells (HSC): effect of canrenone. J Hepatol . 2001; 34(Suppl 1) 84[Abst]
50 Parola M, Robino G, Marra F. HNE interacts directly with JNK isoforms in human hepatic stellate cells. J Clin Invest . 1998; 102 1942-1950
51 Robino G, Parola M, Marra F. Interaction between 4-hydroxy-2,3-alkenals and the PDGF-β receptor. Reduced tyrosine phosphorylation and downstream signaling in hepatic stellate cells. J Biol Chem . 2000; 275 40561-40567
52 Fibbi G, Pucci M, Grappone C. Functions of the fibrinolytic system in human Ito cells and its control by basic fibroblast and platelet-derived growth factor. Hepatology . 1999; 29 868-878
53 Napoli J, Prentice D, Niinami C, Bishop G A, Desmond P, McCaughan G W. Sequential increases in the intrahepatic expression of epidermal growth factor, basic fibroblast growth factor, and transforming growth factor beta in a bile duct ligated rat model of cirrhosis. Hepatology . 1997; 26 624-633
54 Delrieu I. The high molecular weight isoforms of basic fibroblast growth factor (FGF-2): an insight into an intracrine mechanism. FEBS Lett . 2000; 468 6-10
55 Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res . 2001; 49 568-581
56 Ishikawa K, Mochida S, Mashiba S. Expressions of vascular endothelial growth factor in nonparenchymal as well as parenchymal cells in rat liver after necrosis. Biochem Biophys Res Commun . 1999; 254 587-593
57 Ankoma-Sey V, Matli M, Chang K B. Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene . 1998; 17 115-121
58 Mashiba S, Mochida S, Ishikawa K. Inhibition of hepatic stellate cell contraction during activation in vitro by vascular endothelial growth factor in association with upregulation of FLT tyrosine kinase receptor family, FLT-1. Biochem Biophys Res Commun . 1999; 258 674-678
59 Ankoma-Sey V, Wang Y, Dai Z. Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells. Hepatology . 2000; 31 141-148
60 Branton M H, Kopp J B. TGF-β and fibrosis. Microbes Infect . 1999; 1 1349-1365
61 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
62 Nakatsukasa H, Nagy P, Evarts R P, Hsia C C, Marsden E, Thorgeirsson S S. Cellular distribution of transforming growth factor-beta 1 and procollagen types I, III, and IV transcripts in carbon tetrachloride-induced rat liver fibrosis. J Clin Invest . 1990; 85 1833-1843
63 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
64 Sanderson N, Factor V, Nagy P. Hepatic expression of mature transforming growth factor beta 1 in transgenic mice results in multiple tissue lesions. Proc Natl Acad Sci USA . 1995; 92 2572-2576
65 George J, Roulot D, Koteliansky V E, Bissell D M. 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 USA . 1999; 96 12719-12724
66 Friedman S L. Cytokines and fibrogenesis. Semin Liver Dis . 1999; 19 129-140
67 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 myofibroblast-like cells. A potential mechanism of self perpetuation in liver fibrogenesis. J Clin Invest . 1992; 89 19-27
68 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
69 Win K M, Charlotte F, Mallat A. Mitogenic effect of transforming growth factor-beta 1 on huma n Ito cells in culture: evidence for mediation by endogenous platelet-derived growth factor. Hepatology . 1993; 18 137-145
70 Piek E, Heldin C H, Ten Dijke P. Specificity, diversity, and regulation in TGF-beta superfamily signaling. FASEB J . 1999; 13 2105-2124
71 Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol . 2000; 1 169-178
72 Ashcroft G S, Yang X, Glick A B. Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response. Nat Cell Biol . 1999; 1 260-266
73 Saitoh M, Nishitoh H, Amagasa T. Identification of important regions in the cytoplasmic juxtamembrane domain of type I receptor that separate signaling pathways of transforming growth factor-beta. J Biol Chem . 1996; 271 2769-2775
74 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
75 Roulot D, Sevcsik A M, Coste T, Strosberg A D, Marullo S. Role of transforming growth factor beta type II receptor in hepatic fibrosis: studies of human chronic hepatitis C and experimental fibrosis in rats. Hepatology . 1999; 29 1730-1738
76 Massague J. TGF-β signal transduction. Annu Rev Biochem . 1998; 67 753-759
77 Dooley S, Delvoux B, Lahme B. Modulation of transforming growth factor beta response and signaling during transdifferentiation of rat hepatic stellate cells to myofibroblasts. Hepatology . 2000; 31 1094-1106
78 Inoue T, Thomas J H. Suppressors of transforming growth factor-beta pathway mutants in the Caenorhabditis elegans dauer formation pathway. Genetics . 2000; 156 1035-1046
79 Inagaki Y, Truter S, Ramirez F. Transforming growth factor-beta stimulates alpha 2(I) collagen gene expression through a cis-acting element that contains an Sp1-binding site. J Biol Chem . 1994; 269 14828-14834
80 Inagaki Y, Nemoto T, Nakao A. Interaction between GC box binding factors and Smad proteins modulates cell lineage-specific alpha 2(I) collagen gene transcription. J Biol Chem . 2001; 276 16573-16579
81 Inagaki Y, Mamura M, Kanamaru Y. Constitutive phosphorylation and nuclear localization of Smad3 are correlated with increased collagen gene transcription in activated hepatic stellate cells. J Cell Physiol . 2001; 187 117-123
82 Reimann T, Hempel U, Krautwald 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
83 Davis B H, Chen A P, Beno D WA. Raf and mitogen-activated protein kinase regulate stellate cell collagen gene expression. J Biol Chem . 1996; 271 11039-11042
84 Anania F A, Potter J J, Rennie-Tankersley L, Mezey E. Activation by acetaldehyde of the promoter of the mouse alpha2(I) collagen gene when transfected into rat activated stellate cells. Arch Biochem Biophys . 1996; 331 187-193
85 Armendariz-Borunda J, Simkevich C P, Roy N, Raghow R, Kang A H, Seyer J M. Activation of Ito cells involves regulation of AP-1 binding proteins and induction of type I collagen gene expression. Biochem J . 1994; 304 817-824
86 Garcia-Trevijano E R, Iraburu M J, Fontana L. Transforming growth factor beta1 induces the expression of alpha1(I) procollagen mRNA by a hydrogen peroxide-C/EBPbeta-dependent mechanism in rat hepatic stellate cells. Hepatology . 1999; 29 960-970
87 De Bleser J P, Xu G, Rombouts K, Rogiers V, Geerts A. Glutathione levels discriminate between oxidative stress and transforming growth factor-beta signaling in activated rat hepatic stellate cells. J Biol Chem . 1999; 274 33881-33887
88 Sugiyama M, Ichida T, Sato T. Expression of activin A is increased in cirrhotic and fibrotic rat livers. Gastroenterology . 1998; 114 550-558
89 Yanagisawa M, Masaki T. Endothelin, a novel endothelium-derived peptide. Biochem Pharmacol . 1989; 38 1877-1883
90 Simonson M S, Dunn M J. Endothelins: a family of regulatory peptides. Hypertension . 1991; 17 856-863
91 Simonson M S. Endothelins: multifunctional renal peptides. Physiol Rev . 1993; 73 375-411
92 Masaki T, Ninomiya H, Sakamoto A, Okamoto Y. Structural basis of the function of endothelin receptor. Mol Cell Biochem . 1999; 190 153-156
93 Gandhi C R, Stephenson K, Olson M S. Endothelin, a potent peptide agonist in the liver. J Biol Chem . 1990; 265 17432-17435
94 Roden M, Vierhapper H, Liener K, Waldhausl W. Endothelin-1- stimulated glucose production in vitro in the isolated perfused rat liver. Metabolism . 1992; 41 290-295
95 Thran-Thi T-A, Kawada N, Decker K. Regulation of endothelin-1 action on the perfused rat liver. FEBS Lett . 1993; 318 353-357
96 Gandhi C R, Behal R H, Harvey S A, Nouchi T A, Olson M S. Hepatic effects of endothelin. Receptor characterization and endothelin-induced signal transduction in hepatocytes. Biochem J . 1992; 287 897-904
97 Serradeil-Le Gal C, Jouneaux C, Sanchez-Bueno A. Endothelin action in rat liver. Receptors, free Ca²⁺ oscillations, and activation of glycogenolysis. J Clin Invest . 1991; 87 133-138
98 Pinzani M, Milani S, DeFranco R. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology . 1996; 110 534-548
99 Alam I, Bass N M, Bacchetti P, Gee L, Rockey D C. Hepatic tissue endothelin-1 levels in chronic liver disease correlate with disease severity and ascites. Am J Gastroenterol . 2000; 95 199-203
100 Tieche S, De Gottardi A, Kappeler A. Overexpression of endothelin-1 in bile duct ligated rats: correlation with activation of hepatic stellate cells and portal pressure. J Hepatol . 2001; 34 38-45
101 Rockey D C, Fouassier L, Chung J J, 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
102 Leivas A, Jimenez W, Bruix J. Gene expression of endothelin-1 and ET(A) and ET(B) receptors in human cirrhosis: relationship with hepatic hemodynamics. J Vasc Res . 1998; 35 186-193
103 Rieder H, Ramadori G, Meyer zum Buschenfelde H K. Sinusoidal endothelial liver cells in vitro release endothelin: augmentation by transforming growth factor β and Kupffer cell-conditioned media. Klin Wochenschr . 1991; 69 387-391
104 Housset C N, 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
105 Gabriel A, Kuddus R H, Rao A S, Watkins W D, Gandhi C R. Superoxide-induced changes in endothelin (ET) receptors in hepatic stellate cells. J Hepatol . 1998; 29 614-627
106 Shao R, Yan W, Rockey D C. Regulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during wound healing. J Biol Chem . 1999; 274 3228-3234
107 Reinehr R M, Kubitz R, Peters-Regehr T, Bode J G, Haussinger D. Activation of rat hepatic stellate cells in culture is associated with increased sensitivity to endothelin 1. Hepatology . 1998; 28 1566-1577
108 Wang Y Z, Pouyssegur J, Dunn M J. Endothelin stimulates mitogen-activated protein kinase activity in mesangial cells through ET(A). J Am Soc Nephrol . 1994; 5 1074-1080
109 Mallat A, Fouassier F, Preaux A M. Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells: an endothelin B receptor-mediated pathway. J Clin Invest . 1995; 96 42-49
110 Gallois C, Habib A, Tao J. Role of NF-kappaB in the antiproliferative effect of endothelin-1 and tumor necrosis factor-alpha in human hepatic stellate cells. Involvement of cyclooxygenase-2. J Biol Chem . 1998; 273 23183-23190
111 Gabriel A, Kuddus R H, Rao A S, Gandhi C R. Down-regulation of endothelin receptors by transforming growth factor beta1 in hepatic stellate cells. J Hepatol . 1999; 30 440-450
112 Gandhi C R, Uemura T, Kuddus R. Endotoxin causes up-regulation of endothelin receptors in cultured hepatic stellate cells via nitric oxide-dependent and -independent mechanisms. Br J Pharmacol . 2000; 131 319-327
113 Pinzani M, Failli P, Ruocco C. Fat-storing cells as liver-specific pericytes: spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest . 1992; 90 642-646
114 Tangkijvanich P, Tam S P, Yee H F. Wound-induced migration of rat hepatic stellate cells is modulated by endothelin-1 through rho-kinase-mediated alterations in the acto-myosin cytoskeleton. Hepatology . 2001; 33 74-80
115 Rockey D C, Chung J J. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest . 1996; 98 1381-1388
116 Poo J L, Jimenez W, Maria Munoz R. Chronic blockade of endothelin receptors in cirrhotic rats: hepatic and hemodynamic effects. Gastroenterology . 1999; 116 161-167
117 Cho J J, Hocher B, Herbst H. An oral endothelin-A receptor antagonist blocks collagen synthesis and deposition in advanced rat liver fibrosis. Gastroenterology . 2000; 118 1169-1178
118 Caligiuri A, Glaser S, Rodgers R E. Endothelin-1 inhibits secretin-stimulated ductal secretion by interacting with ETA receptors on large cholangiocytes. Am J Physiol . 1998; 275 G835-G846
119 Bataller R, Gines P, Nicolas J M. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology . 2000; 118 1149-1156
120 Lim D S, Lutucuta S, Bachireddy P. Angiotensin II blockade reverses myocardial fibrosis in a transgenic mouse model of human hypertrophic cardiomyopathy. Circulation . 2001; 103 789-791
121 Bataller R, Nicolas J M, Gines P. Arginine vasopressin induces contraction and stimulates growth of cultured human hepatic stellate cells. Gastroenterology . 1997; 113 615-624
122 Coughlin S R. Thrombin signalling and protease-activated receptors. Nature . 2000; 407 258-264
123 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
124 Marra F, DeFranco R, Grappone C. Expression of the thrombin receptor in human liver: up-regulation during acute and chronic injury. Hepatology . 1998; 27 462-471
125 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
126 Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol . 2000; 18 217-242
127 Marra F. Hepatic stellate cells and the regulation of liver inflammation. J Hepatol . 1999; 31 1120-1130
128 Romagnani P, Beltrame C, Annunziato F. Role for interactions between IP-10/Mig and CXCR3 in proliferative glomerulonephritis. J Am Soc Nephrol . 1999; 10 2518-2526
129 Gerard C, Rollins B J. Chemokines and disease. Nat Immunol . 2001; 2 108-115
130 Schweickart V L, Epp A, Raport C J, Gray P W. CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J Biol Chem . 2000; 275 9550-9556
131 Ashkenazi A, Dixit V M. Death receptors: signaling and modulation. Science . 1998; 281 1305-1308
132 Ledgerwood E C, Pober J S, Bradley J R. Recent advances in the molecular basis of TNF signal transduction. Lab Invest . 1999; 79 1041-1050
133 Rothe J, Lesslauer W, Loetscher H. Mice lacking the tumour necrosis factor receptor-1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes Nature . 1993; 364 798-802
134 Knittel T, Muller L, Saile B, Ramadori G. Effect of tumour necrosis factor-alpha on proliferation, activation and protein synthesis of rat hepatic stellate cells. J Hepatol . 1997; 27 1067-1080
135 Armendariz-Borunda J, Katayama K, Seyer J M. Transcriptional mechanisms of type I collagen gene expression are differentially regulated by interleukin-1 beta, tumor necrosis factor alpha, and transforming growth factor beta in Ito cells. J Biol Chem . 1992; 267 14316-14321
136 Gallois C, Habib A, Tao J. Role of NF-kappaB in the antiproliferative effect of endothelin-1 and tumor necrosis factor-alpha in human hepatic stellate cells. Involvement of cyclooxygenase-2. J Biol Chem . 1998; 273 23183-23190
137 Hellerbrand C, Jobin C, Licato L L, Sartor R B, Brenner D A. Cytokines induce NF-kappaB in activated but not in quiescent rat hepatic stellate cells. Am J Physiol . 1998; 275 G269-278
138 Efsen E, Pastacaldi S, Bonacchi A. Agonist-specific regulation of monocyte chemoattractant protein-1 expression by cyclo-oxygenase metabolites in hepatic stellate cells. Hepatology . 2001; 33 713-721
139 Elsharkawy A M, Wright M C, Hay R T, Arthur M J. Persistent activation of nuclear factor-kappaB in cultured rat hepatic stellate cells involves the induction of potentially novel Rel-like factors and prolonged changes in the expression of IkappaB family proteins. Hepatology . 1999; 30 761-769
140 Beg A, Sha W, Bronson R, Ghosh S, Baltimore D. Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-κB. Nature . 1995; 376 167-170
141 Lang A, Schoonhoven R, Tuvia S, Brenner D A, Rippe R A. Nuclear factor kappaB in proliferation, activation, and apoptosis in rat hepatic stellate cells. J Hepatol . 2000; 33 49-58
142 Reeves H L, Dack C L, Peak M, Burt A D, Day C P. Stress-activated protein kinases in the activation of rat hepatic stellate cells in culture. J Hepatol . 2000; 32 465-472
143 Poulos J E, Weber J D, Bellezzo J M. Fibronectin and cytokines increase JNK, ERK, AP-1 activity, and transin gene expression in rat hepatic stellate cells. Am J Physiol . 1997; 273 G804-811
144 Hernandez-Munoz I, de la Torre P, Sanchez-Alcazar J A. Tumor necrosis factor alpha inhibits collagen alpha 1(I) gene expression in rat hepatic stellate cells through a G protein. Gastroenterology . 1997; 113 625-640
145 Houglum K, Buck M, Kim D J, Chojkier M. TNF-alpha inhibits liver collagen-alpha 1(I) gene expression through a tissue-specific regulatory region. Am J Physiol . 1998; 274 G840-847
146 Iraburu M J, Dominguez-Rosales J A, Fontana L. Tumor necrosis factor alpha down-regulates expression of the alpha1(I) collagen gene in rat hepatic stellate cells through a p20C/EBPbeta- and C/EBPdelta-dependent mechanism. Hepatology . 2000; 31 1086-1093
147 Hernandez I, de la Torre P, Rey-Campos J. Collagen alpha1(I) gene contains an element responsive to tumor necrosis factor-alpha located in the 5′ untranslated region of its first exon. DNA Cell Biol . 2000; 19 341-352
148 Saile B, Knittel T, Matthes N, Schott P, Ramadori G. CD95/CD95L-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
149 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
150 Trim N, Morgan S, Evans M. Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation. Am J Pathol . 2000; 156 1235-1243
151 Cassiman D, Denef C, Desmet V J, Roskams T. Human and rat hepatic stellate cells express neurotrophins and neurotrophin receptors. Hepatology . 2001; 33 148-158
152 Schwabe R F, Schnabl B, Kweon Y O, Brenner D A. CD40 activates NF-kappaB and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. J Immunol . 2001; 166 6812-6819
153 Matsuoka M, Pham N T, Tsukamoto H. Differential effects of interleukin-1 alpha, tumor necrosis factor alpha, and transforming growth factor beta 1 on cell proliferation and collagen formation by cultured fat-storing cells. Liver . 1989; 9 71-78
154 Mancini R, Benedetti A, Jezequel A M. An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver. Virchows Arch . 1994; 424 25-31
155 Darnell Jr E J. STATs and gene regulation. Science . 1997; 277 1630-1633
156 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
157 Ramadori G, Knittel T, Odenthal M, Schwogler S, Neubauer K, Meyer zum Buschenfelde H K. Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: regulation by cytokines. Gastroenterology . 1992; 103 1313-1321
158 Mallat A, Preaux A M, Blazejewski S, Rosenbaum J, Dhumeaux D, Mavier P. Interferon alfa and gamma inhibit proliferation and collagen synthesis of human Ito cells in culture. Hepatology . 1995; 21 1003-1010
159 Rockey D C, Chung J J. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J Invest Med . 1994; 42 660-670
160 Rockey D C, Chung J J. Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J Invest Med . 1994; 42 660-670
161 Gressner A M, Althaus M. Effects of murine recombinant interferon-gamma on rat liver fat storing cell proliferation, cluster formation and proteoglycan synthesis. Biochem Pharmacol . 1990; 40 1953-1962
162 Greenwel P, Iraburu M J, Reyes-Romero M. Induction of an acute phase response in rats stimulates the expression of alpha1(I) procollagen messenger ribonucleic acid in their livers. Possible role of interleukin-6. Lab Invest . 1995; 72 83-91
163 Wang S C, Ohata M, Schrum L, Rippe R A, Tsukamoto H. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J Biol Chem . 1998; 273 302-308
164 Levy M T, Trojanowska M, Reuben A. Oncostatin M: a cytokine upregulated in human cirrhosis, increases collagen production by human hepatic stellate cells. J Hepatol . 2000; 32 218-226
165 Carloni V, Romanelli R G, Pinzani M. Expression and function of integrins receptors for collagen and laminin in cultured human hepatic stellate cells. Gastroenterology . 1996; 110 1127-1136
166 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
167 Burridge K, Turner C E, Romer L H. Tyrosine phosphorylation of paxillin and pp125 FAK accompanies cell adhesion to extracellular matrix: a role in cytoskeletal assembly. J Cell Biol . 1992; 119 893-903
168 Schaller M D, Parsons J T. Focal adhesion kinase: an integrin-linked protein tyrosine kinase. Trends Cell Biol . 1993; 3 258-262
169 Schaller M D, Otey C A, Hildebrand J D, Parsons J T. Focal adhesion kinase and paxillin bind to peptides mimicking β integrin cytoplasmic domains. J Cell Biol . 1995; 130 1181-1187
170 Carloni V, Romanelli R G, Pinzani M, Laffi G, Gentilini P. Focal adhesion kinase and phospholipase Cγ involvement in adhesion and migration of human hepatic stellate cells. Gastroenterology . 1997; 112 522-531
171 Huang S, Ingber D E. The structural and mechanical complexity of cell-growth control. Nat Cell Biol . 1999; 1 E131-138