Cytokines and Renin-Angiotensin System Signaling in Hepatic Fibrosis

Clinics in Liver Disease

Volumn 12, Issue 4, 2008, Pages 825-852

  Moreno, Montserrat ^a   Bataller, Ramon ^a  

^a HOSPITAL CLÍNIC   (Spain)

Author keywords

Angiotensin II; Cytokines; Hepatic stellate cells; Liver fibrosis; Renin angiotensin system

Indexed keywords

ADIPOCYTOKINE; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ANGIOTENSIN II; BETA CATENIN; CANDESARTAN; CANDESARTAN HEXETIL; CANNABINOID; CAPTOPRIL; CYTOKINE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENALAPRIL; GROWTH FACTOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRBESARTAN; JANUS KINASE; LISINOPRIL; LOSARTAN; MITOGEN ACTIVATED PROTEIN KINASE; OLMESARTAN; PERINDOPRIL; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMAD PROTEIN; STAT PROTEIN; TELMISARTAN; VALSARTAN; VASOACTIVE AGENT; WNT PROTEIN;

CLINICAL TRIAL; COLLAGEN SYNTHESIS; CYTOKINE RELEASE; FIBROGENESIS; HEPATITIS C; HUMAN; HYPOTENSION; INFLAMMATORY CELL; KIDNEY DISEASE; LIVER CELL; LIVER FIBROSIS; LIVER INJURY; LIVER TOXICITY; MOLECULAR DYNAMICS; NONHUMAN; PROTEIN FUNCTION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; STELLATE CELL; UNSPECIFIED SIDE EFFECT;

ANGIOTENSIN II; ANIMALS; COLLAGEN; CYTOKINES; HEPATIC STELLATE CELLS; HUMANS; LIVER CIRRHOSIS; RENIN-ANGIOTENSIN SYSTEM; SIGNAL TRANSDUCTION;

EID: 54549098072     PISSN: 10893261     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cld.2008.07.013     Document Type: Review

References (176)

1. Bataller R., and Brenner D.A. Liver fibrosis. J Clin Invest 115 2 (2005) 209-218
2. Saile B., and Ramadori G. Inflammation, damage repair and liver fibrosis-role of cytokines and different cell types. Z Gastroenterol 45 1 (2007) 77-86
3. Schuppan D., Krebs A., Bauer M., et al. Hepatitis C and liver fibrosis. Cell Death Differ 10 Suppl 1 (2003) S59-S67
4. Reuben A. Alcohol and the liver. Curr Opin Gastroenterol 24 3 (2008) 328-338
5. Marra F., Aleffi S., Bertolani C., et al. Adipokines and liver fibrosis. Eur Rev Med Pharmacol Sci 9 5 (2005) 279-284
6. Pinzani M., and Marra F. Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 21 3 (2001) 397-416
7. Bataller R., Sancho-Bru P., Gines P., et al. Liver fibrogenesis: a new role for the renin-angiotensin system. Antioxid Redox Signal 7 9-10 (2005) 1346-1355
8. Bataller R., Sancho-Bru P., Gines P., et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology 125 1 (2003) 117-125
9. Bataller R., Gines P., Nicolas J.M., et al. Angiotensin II induces contraction and proliferation of human hepatic stellate cells. Gastroenterology 118 6 (2000) 1149-1156
10. Bataller R., Schwabe R.F., Choi Y.H., et al. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 112 9 (2003) 1383-1394
11. Hirose A., Ono M., Saibara T., et al. Angiotensin II type 1 receptor blocker inhibits fibrosis in rat nonalcoholic steatohepatitis. Hepatology 45 6 (2007) 1375-1381
12. Jin H., Yamamoto N., Uchida K., et al. Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet. Biochem Biophys Res Commun 364 4 (2007) 801-807
13. Jonsson J.R., Clouston A.D., Ando Y., et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 121 1 (2001) 148-155
14. Ramalho L.N., Ramalho F.S., Zucoloto S., et al. Effect of losartan, an angiotensin II antagonist, on secondary biliary cirrhosis. Hepatogastroenterology 49 48 (2002) 1499-1502
15. Friedman S.L. Mechanisms of hepatic fibrogenesis. Gastroenterology 134 6 (2008) 1655-1669
16. Rockey D.C., and Chung J.J. Endothelin antagonism in experimental hepatic fibrosis. Implications for endothelin in the pathogenesis of wound healing. J Clin Invest 98 6 (1996) 1381-1388
17. Shi Z., Wakil A.E., and Rockey D.C. Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses. Proc Natl Acad Sci U S A 94 20 (1997) 10663-10668
18. Galliera E., Corsi M.M., Bonecchi R., et al. Chemokines as pharmacological targets. Mini Rev Med Chem 8 7 (2008) 638-646
19. Hernandez-Munoz I., de la T.P., Sanchez-Alcazar J.A., et al. Tumor necrosis factor alpha inhibits collagen alpha 1(I) gene expression in rat hepatic stellate cells through a G protein. Gastroenterology 113 2 (1997) 625-640
20. Eng F.J., and Friedman S.L. Transcriptional regulation in hepatic stellate cells. Semin Liver Dis 21 3 (2001) 385-395
21. Han Y.P., Zhou L., Wang J., et al. Essential role of matrix metalloproteinases in interleukin-1-induced myofibroblastic activation of hepatic stellate cell in collagen. J Biol Chem 279 6 (2004) 4820-4828
22. Mancini R., Benedetti A., and Jezequel A.M. An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver. Virchows Arch 424 1 (1994) 25-31
23. Zhang L.J., Zheng W.D., Chen Y.X., et al. Antifibrotic effects of interleukin-10 on experimental hepatic fibrosis. Hepatogastroenterology 54 79 (2007) 2092-2098
24. Zhang L.J., Chen Y.X., Chen Z.X., et al. Effect of interleukin-10 and platelet-derived growth factor on expressions of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinases-1 in rat fibrotic liver and cultured hepatic stellate cells. World J Gastroenterol 10 17 (2004) 2574-2579
25. Giannelli G., Bergamini C., Marinosci F., et al. Antifibrogenic effect of IFN-alpha2b on hepatic stellate cell activation by human hepatocytes. J Interferon Cytokine Res 26 5 (2006) 301-308
26. Chang X.M., Chang Y., and Jia A. Effects of interferon-alpha on expression of hepatic stellate cell and transforming growth factor-beta1 and alpha-smooth muscle actin in rats with hepatic fibrosis. World J Gastroenterol 11 17 (2005) 2634-2636
27. Inagaki Y., Nemoto T., Kushida M., et al. Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice. Hepatology 38 4 (2003) 890-899
28. Wu C.S., Piao X.X., Piao D.M., et al. Treatment of pig serum-induced rat liver fibrosis with Boschniakia rossica, oxymatrine and interferon-alpha. World J Gastroenterol 11 1 (2005) 122-126
29. Shen H., Zhang M., Minuk G.Y., et al. Different effects of rat interferon alpha, beta and gamma on rat hepatic stellate cell proliferation and activation. BMC Cell Biol 3 (2002) 9
30. Yoshiji H., Kuriyama S., Noguchi R., et al. Combination of interferon-beta and angiotensin-converting enzyme inhibitor, perindopril, attenuates the murine liver fibrosis development. Liver Int 25 1 (2005) 153-161
31. 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 152 2 (1998) 423-430
32. Marra F., Romanelli R.G., Giannini C., et al. Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells. Hepatology 29 1 (1999) 140-148
33. Tsuruta S., Nakamuta M., Enjoji M., et al. Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. Int J Mol Med 14 5 (2004) 837-842
34. Nischalke H.D., Nattermann J., Fischer H.P., et al. Semiquantitative analysis of intrahepatic CC-chemokine mRNas in chronic hepatitis C. Mediators Inflamm 13 5-6 (2004) 357-359
35. Schwabe R.F., Bataller R., and Brenner D.A. Human hepatic stellate cells express CCR5 and RANTES to induce proliferation and migration. Am J Physiol Gastrointest Liver Physiol 285 5 (2003) G949-G958
36. Swiatkowska-Stodulska R., Bakowska A., and Drobinska-Jurowiecka A. Interleukin-8 in the blood serum of patients with alcoholic liver disease. Med Sci Monit 12 5 (2006) CR215-CR220
37. Yamashiki M., Kosaka Y., Nishimura A., et al. Analysis of serum cytokine levels in primary biliary cirrhosis patients and healthy adults. J Clin Lab Anal 12 2 (1998) 77-82
38. Colmenero J., Bataller R., Sancho-Bru P., et al. Hepatic expression of candidate genes in patients with alcoholic hepatitis: correlation with disease severity. Gastroenterology 132 2 (2007) 687-697
39. Li X., Ponten A., Aase K., et al. PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol 2 5 (2000) 302-309
40. LaRochelle W.J., Jeffers M., McDonald W.F., et al. PDGF-D, a new protease-activated growth factor. Nat Cell Biol 3 5 (2001) 517-521
41. Pinzani M., Gesualdo L., Sabbah G.M., et al. 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 84 6 (1989) 1786-1793
42. Borkham-Kamphorst E., van Roeyen C.R., Ostendorf T., et al. Pro-fibrogenic potential of PDGF-D in liver fibrosis. J Hepatol 46 6 (2007) 1064-1074
43. Pinzani M., Milani S., Herbst H., et al. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis. Am J Pathol 148 3 (1996) 785-800
44. Wong L., Yamasaki G., Johnson R.J., et al. Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture. J Clin Invest 94 4 (1994) 1563-1569
45. Borkham-Kamphorst E., Stoll D., Gressner A.M., et al. Antisense strategy against PDGF B-chain proves effective in preventing experimental liver fibrogenesis. Biochem Biophys Res Commun 321 2 (2004) 413-423
46. Borkham-Kamphorst E., Herrmann J., Stoll D., et al. Dominant-negative soluble PDGF-beta receptor inhibits hepatic stellate cell activation and attenuates liver fibrosis. Lab Invest 84 6 (2004) 766-777
47. De Bleser P.J., Niki T., Rogiers V., et al. Transforming growth factor-beta gene expression in normal and fibrotic rat liver. J Hepatol 26 4 (1997) 886-893
48. Shek F.W., and Benyon R.C. How can transforming growth factor beta be targeted usefully to combat liver fibrosis?. Eur J Gastroenterol Hepatol 16 2 (2004) 123-126
49. Chen H.N., Fan S., and Weng C.F. Down-regulation of TGFbeta1 and leptin ameliorates thioacetamide-induced liver injury in lipopolysaccharide-primed rats. J Endotoxin Res 13 3 (2007) 176-188
50. Onichtchouk D., Chen Y.G., Dosch R., et al. Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature 401 6752 (1999) 480-485
51. Seki E., De Minicis S., Osterreicher C.H., et al. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat Med 13 11 (2007) 1324-1332
52. Novo E., Cannito S., Zamara E., et al. Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol 170 6 (2007) 1942-1953
53. Yoshiji H., Kuriyama S., Yoshii J., et al. Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis. Gut 52 9 (2003) 1347-1354
54. Yu C., Wang F., Jin C., et al. Role of fibroblast growth factor type 1 and 2 in carbon tetrachloride-induced hepatic injury and fibrogenesis. Am J Pathol 163 4 (2003) 1653-1662
55. Canturk N.Z., Canturk Z., Ozden M., et al. Protective effect of IGF-1 on experimental liver cirrhosis-induced common bile duct ligation. Hepatogastroenterology 50 54 (2003) 2061-2066
56. Sanz S., Pucilowska J.B., Liu S., et al. Expression of insulin-like growth factor I by activated hepatic stellate cells reduces fibrogenesis and enhances regeneration after liver injury. Gut 54 1 (2005) 134-141
57. Xia J.L., Dai C., Michalopoulos G.K., et al. Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. Am J Pathol 168 5 (2006) 1500-1512
58. Rockey D.C., and Chung J.J. Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension. Gastroenterology 114 2 (1998) 344-351
59. Hui A.Y., Dannenberg A.J., Sung J.J., et al. Prostaglandin E2 inhibits transforming growth factor beta 1-mediated induction of collagen alpha 1(I) in hepatic stellate cells. J Hepatol 41 2 (2004) 251-258
60. Koide S., Kobayashi Y., Oki Y., et al. Prostaglandin E2 inhibits platelet-derived growth factor-stimulated cell proliferation through a prostaglandin E receptor EP2 subtype in rat hepatic stellate cells. Dig Dis Sci 49 9 (2004) 1394-1400
61. Fiorucci S., Antonelli E., Distrutti E., et al. PAR1 antagonism protects against experimental liver fibrosis. Role of proteinase receptors in stellate cell activation. Hepatology 39 2 (2004) 365-375
62. Duplantier J.G., Dubuisson L., Senant N., et al. A role for thrombin in liver fibrosis. Gut 53 11 (2004) 1682-1687
63. Rullier A., Gillibert-Duplantier J., Costet P., et al. Protease-activated receptor 1 knockout reduces experimentally induced liver fibrosis. Am J Physiol Gastrointest Liver Physiol 294 1 (2008) G226-G235
64. Pinzani M., Milani S., De Franco R., et al. Endothelin 1 is overexpressed in human cirrhotic liver and exerts multiple effects on activated hepatic stellate cells. Gastroenterology 110 2 (1996) 534-548
65. Poo J.L., Jimenez W., Maria M.R., et al. Chronic blockade of endothelin receptors in cirrhotic rats: hepatic and hemodynamic effects. Gastroenterology 116 1 (1999) 161-167
66. Oben J.A., Yang S., Lin H., et al. Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells. Biochem Biophys Res Commun 302 4 (2003) 685-690
67. Sancho-Bru P., Bataller R., Colmenero J., et al. Norepinephrine induces calcium spikes and proinflammatory actions in human hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 291 5 (2006) G877-G884
68. Bertolani C., Sancho-Bru P., Failli P., et al. Resistin as an intrahepatic cytokine: overexpression during chronic injury and induction of proinflammatory actions in hepatic stellate cells. Am J Pathol 169 6 (2006) 2042-2053
69. Marra F. Leptin and liver fibrosis: a matter of fat. Gastroenterology 122 5 (2002) 1529-1532
70. Ikejima K., Takei Y., Honda H., et al. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 122 5 (2002) 1399-1410
71. Kamada Y., Tamura S., Kiso S., et al. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology 125 6 (2003) 1796-1807
72. Siegmund S.V., and Schwabe R.F. Endocannabinoids and liver disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis. Am J Physiol Gastrointest Liver Physiol 294 2 (2008) G357-G362
73. Teixeira-Clerc F., Julien B., Grenard P., et al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 12 6 (2006) 671-676
74. Julien B., Grenard P., Teixeira-Clerc F., et al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 128 3 (2005) 742-755
75. Hezode C., Roudot-Thoraval F., Nguyen S., et al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 42 1 (2005) 63-71
76. Gabele E., Reif S., Tsukada S., et al. The role of p70S6K in hepatic stellate cell collagen gene expression and cell proliferation. J Biol Chem 280 14 (2005) 13374-13382
77. Reif S., Lang A., Lindquist J.N., et al. The role of focal adhesion kinase-phosphatidylinositol 3-kinase-akt signaling in hepatic stellate cell proliferation and type I collagen expression. J Biol Chem 278 10 (2003) 8083-8090
78. Aleffi S., Petrai I., Bertolani C., et al. Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42 6 (2005) 1339-1348
79. Lechuga C.G., Hernandez-Nazara Z.H., Hernandez E., et al. PI3K is involved in PDGF-beta receptor upregulation post-PDGF-BB treatment in mouse HSC. Am J Physiol Gastrointest Liver Physiol 291 6 (2006) G1051-G1061
80. Pinzani M. PDGF and signal transduction in hepatic stellate cells. Front Biosci 7 (2002) d1720-d1726
81. Zhang X., Jin B., and Huang C. The PI3K/Akt pathway and its downstream transcriptional factors as targets for chemoprevention. Curr Cancer Drug Targets 7 4 (2007) 305-316
82. Zhu J., Wu J., Frizell E., et al. Rapamycin inhibits hepatic stellate cell proliferation in vitro and limits fibrogenesis in an in vivo model of liver fibrosis. Gastroenterology 117 5 (1999) 1198-1204
83. Goldsmith Z.G., and Dhanasekaran D.N. G protein regulation of MAPK networks. Oncogene 26 22 (2007) 3122-3142
84. Bonacchi A., Romagnani P., Romanelli R.G., et al. Signal transduction by the chemokine receptor CXCR3: activation of Ras/ERK, Src, and phosphatidylinositol 3-kinase/Akt controls cell migration and proliferation in human vascular pericytes. J Biol Chem 276 13 (2001) 9945-9954
85. Bataller R., Gabele E., Schoonhoven R., et al. Prolonged infusion of angiotensin II into normal rats induces stellate cell activation and proinflammatory events in liver. Am J Physiol Gastrointest Liver Physiol 285 3 (2003) G642-G651
86. Marra F., Arrighi M.C., Fazi M., et al. Extracellular signal-regulated kinase activation differentially regulates platelet-derived growth factor's actions in hepatic stellate cells, and is induced by in vivo liver injury in the rat. Hepatology 30 4 (1999) 951-958
87. Schwabe R.F., Schnabl B., Kweon Y.O., et al. CD40 activates NF-kappa B and c-Jun N-terminal kinase and enhances chemokine secretion on activated human hepatic stellate cells. J Immunol 166 11 (2001) 6812-6819
88. Schwabe R.F., Uchinami H., Qian T., et al. Differential requirement for c-Jun NH2-terminal kinase in TNFalpha- and Fas-mediated apoptosis in hepatocytes. FASEB J 18 6 (2004) 720-722
89. Schnabl B., Bradham C.A., Bennett B.L., et al. TAK1/JNK and p38 have opposite effects on rat hepatic stellate cells. Hepatology 34 5 (2001) 953-963
90. Tsukada S., Westwick J.K., Ikejima K., et al. SMAD and p38 MAPK signaling pathways independently regulate alpha1(I) collagen gene expression in unstimulated and transforming growth factor-beta-stimulated hepatic stellate cells. J Biol Chem 280 11 (2005) 10055-10064
91. Tsukada S., Parsons C.J., and Rippe R.A. Mechanisms of liver fibrosis. Clin Chim Acta 364 1-2 (2006) 33-60
92. Shi Y.F., Fong C.C., Zhang Q., et al. Hypoxia induces the activation of human hepatic stellate cells LX-2 through TGF-beta signaling pathway. FEBS Lett 581 2 (2007) 203-210
93. Cohen Jr. M.M. TGF beta/Smad signaling system and its pathologic correlates. Am J Med Genet A 116A 1 (2003) 1-10
94. Weng H., Mertens P.R., Gressner A.M., et al. IFN-gamma abrogates profibrogenic TGF-beta signaling in liver by targeting expression of inhibitory and receptor Smads. J Hepatol 46 2 (2007) 295-303
95. Kaimori A., Potter J., Kaimori J.Y., et al. Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro. J Biol Chem 282 30 (2007) 22089-22101
96. Seyhan H., Hamzavi J., Wiercinska E., et al. Liver fibrogenesis due to cholestasis is associated with increased Smad7 expression and Smad3 signaling. J Cell Mol Med 10 4 (2006) 922-932
97. Inagaki Y., Kushida M., Higashi K., et al. Cell type-specific intervention of transforming growth factor beta/Smad signaling suppresses collagen gene expression and hepatic fibrosis in mice. Gastroenterology 129 1 (2005) 259-268
98. Schwabe R.F., and Brenner D.A. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol 290 4 (2006) G583-G589
99. Hellerbrand C., Jobin C., Licato L.L., et al. Cytokines induce NF-kappaB in activated but not in quiescent rat hepatic stellate cells. Am J Phys 275 2 Pt 1 (1998) G269-G278
100. Lang A., Schoonhoven R., Tuvia S., et al. Nuclear factor kappaB in proliferation, activation, and apoptosis in rat hepatic stellate cells. J Hepatol 33 1 (2000) 49-58
101. Haughton E.L., Tucker S.J., Marek C.J., et al. Pregnane X receptor activators inhibit human hepatic stellate cell transdifferentiation in vitro. Gastroenterology 131 1 (2006) 194-209
102. Wright M.C. The impact of pregnane X receptor activation on liver fibrosis. Biochem Soc Trans 34 Pt 6 (2006) 1119-1123
103. Marek C.J., Tucker S.J., Konstantinou D.K., et al. Pregnenolone-16alpha-carbonitrile inhibits rodent liver fibrogenesis via PXR (pregnane X receptor)-dependent and PXR-independent mechanisms. Biochem J 387 Pt 3 (2005) 601-608
104. Hellemans K., Michalik L., Dittie A., et al. Peroxisome proliferator-activated receptor-beta signaling contributes to enhanced proliferation of hepatic stellate cells. Gastroenterology 124 1 (2003) 184-201
105. Marra F., Efsen E., Romanelli R.G., et al. Ligands of peroxisome proliferator-activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. Gastroenterology 119 2 (2000) 466-478
106. Galli A., Crabb D.W., Ceni E., et al. Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. Gastroenterology 122 7 (2002) 1924-1940
107. Hellemans K., Rombouts K., Quartier E., et al. PPARbeta regulates vitamin A metabolism-related gene expression in hepatic stellate cells undergoing activation. J Lipid Res 44 2 (2003) 280-295
108. Zhao C., Chen W., Yang L., et al. PPARgamma agonists prevent TGFbeta1/Smad3-signaling in human hepatic stellate cells. Biochem Biophys Res Commun 350 2 (2006) 385-391
109. Gustafson B., and Smith U. Cytokines promote Wnt signaling and inflammation and impair the normal differentiation and lipid accumulation in 3T3-L1 preadipocytes. J Biol Chem 281 14 (2006) 9507-9516
110. Bowerman B. Cell signaling. Wnt moves beyond the canon. Science 320 5874 (2008) 327-328
111. Myung S.J., Yoon J.H., Gwak G.Y., et al. Wnt signaling enhances the activation and survival of human hepatic stellate cells. FEBS Lett 581 16 (2007) 2954-2958
112. Cheng J.H., She H., Han Y.P., et al. Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis. Am J Physiol Gastrointest Liver Physiol 294 1 (2008) G39-G49
113. Schwabe R.F., Seki E., and Brenner D.A. Toll-like receptor signaling in the liver. Gastroenterology 130 6 (2006) 1886-1900
114. Seki E., and Brenner D.A. Toll-like receptors and adaptor molecules in liver disease: Update. Hepatology 48 1 (2008) 322-335
115. Paik Y.H., Schwabe R.F., Bataller R., et al. Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells. Hepatology 37 5 (2003) 1043-1055
116. Ware C.F. The TNF superfamily-2008. Cytokine Growth Factor Rev 19 3-4 (2008) 183-186
117. Rothe J., Lesslauer W., Lotscher H., et al. Mice lacking the tumour necrosis factor receptor 1 are resistant to TNF-mediated toxicity but highly susceptible to infection by Listeria monocytogenes. Nature 364 6440 (1993) 798-802
118. Gallois C., Habib A., Tao J., et al. 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 273 36 (1998) 23183-23190
119. Varela-Rey M., Montiel-Duarte C., Oses-Prieto J.A., et al. p38 MAPK mediates the regulation of alpha1(I) procollagen mRNA levels by TNF-alpha and TGF-beta in a cell line of rat hepatic stellate cells(1). FEBS Lett 528 1-3 (2002) 133-138
120. Reinehr R., Sommerfeld A., and Haussinger D. CD95 ligand is a proliferative and antiapoptotic signal in quiescent hepatic stellate cells. Gastroenterology 134 5 (2008) 1494-1506
121. Taimr P., Higuchi H., Kocova E., et al. Activated stellate cells express the TRAIL receptor-2/death receptor-5 and undergo TRAIL-mediated apoptosis. Hepatology 37 1 (2003) 87-95
122. Cao Q., Mak K.M., Ren C., et al. Leptin stimulates tissue inhibitor of metalloproteinase-1 in human hepatic stellate cells: respective roles of the JAK/STAT and JAK-mediated H2O2-dependant MAPK pathways. J Biol Chem 279 6 (2004) 4292-4304
123. Gao B. Cytokines, STATs and liver disease. Cell Mol Immunol 2 2 (2005) 92-100
124. Jeong W.I., Park O., Radaeva S., et al. STAT1 inhibits liver fibrosis in mice by inhibiting stellate cell proliferation and stimulating NK cell cytotoxicity. Hepatology 44 6 (2006) 1441-1451
125. Caligiuri A., Bertolani C., Guerra C.T., et al. Adenosine monophosphate-activated protein kinase modulates the activated phenotype of hepatic stellate cells. Hepatology 47 2 (2008) 668-676
126. Adachi M., and Brenner D.A. High molecular weight adiponectin inhibits proliferation of hepatic stellate cells via activation of adenosine monophosphate-activated protein kinase. Hepatology 47 2 (2008) 677-685
127. Lavoie J.L., and Sigmund C.D. Minireview: overview of the renin-angiotensin system-an endocrine and paracrine system. Endocrinology 144 6 (2003) 2179-2183
128. Varagic J., and Frohlich E.D. Local cardiac renin-angiotensin system: hypertension and cardiac failure. J Mol Cell Cardiol 34 11 (2002) 1435-1442
129. Weber M.A. Comparison of type 1 angiotensin II receptor blockers and angiotensin converting enzyme inhibitors in the treatment of hypertension. J Hypertens Suppl 15 6 (1997) S31-S36
130. Miyazawa K., Fukuyama J., Misawa K., et al. Tranilast antagonizes angiotensin II and inhibits its biological effects in vascular smooth muscle cells. Atherosclerosis 121 2 (1996) 167-173
131. Kaschina E., and Unger T. Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press 12 2 (2003) 70-88
132. Kurisu S., Ozono R., Oshima T., et al. Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis. Hypertension 41 1 (2003) 99-107
133. Keidar S., Kaplan M., and Gamliel-Lazarovich A. ACE2 of the heart: from angiotensin I to angiotensin (1-7). Cardiovasc Res 73 3 (2007) 463-469
134. Ma L., and Fogo A.B. Role of angiotensin II in glomerular injury. Semin Nephrol 21 6 (2001) 544-553
135. Brenner B.M., and Zagrobelny J. Clinical renoprotection trials involving angiotensin II-receptor antagonists and angiotensin-converting-enzyme inhibitors. Kidney Int Suppl 83 (2003) S77-S85
136. Pinzani M., Failli P., Ruocco C., et al. Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist-stimulated intracellular calcium transients. J Clin Invest 90 2 (1992) 642-646
137. Kanno K., Tazuma S., Nishioka T., et al. Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression. Dig Dis Sci 50 5 (2005) 942-948
138. Yang L., Bataller R., Dulyx J., et al. Attenuated hepatic inflammation and fibrosis in angiotensin type 1a receptor deficient mice. J Hepatol 43 2 (2005) 317-323
139. Paizis G., Cooper M.E., Schembri J.M., et al. Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver. Gastroenterology 123 5 (2002) 1667-1676
140. Ikura Y., Ohsawa M., Shirai N., et al. Expression of angiotensin II type 1 receptor in human cirrhotic livers: its relation to fibrosis and portal hypertension. Hepatol Res 32 2 (2005) 107-116
141. Komeda K., Jin D., Takai S., et al. Significance of chymase-dependent angiotensin II formation in the progression of human liver fibrosis. Hepatol Res 38 5 (2008) 501-510
142. Kamada Y., Tamura S., Kiso S., et al. Angiotensin II stimulates the nuclear translocation of Smad2 and induces PAI-1 mRNA in rat hepatic stellate cells. Hepatol Res 25 3 (2003) 296-305
143. Kitamura K., Tada S., Nakamoto N., et al. Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis. J Gastroenterol Hepatol 22 11 (2007) 2022-2033
144. De Minicis S., and Brenner D.A. NOX in liver fibrosis. Arch Biochem Biophys 462 2 (2007) 266-272
145. Croquet V., Moal F., Veal N., et al. Hemodynamic and antifibrotic effects of losartan in rats with liver fibrosis and/or portal hypertension. J Hepatol 37 6 (2002) 773-780
146. El Demerdash E., Salam O.M., El Batran S.A., et al. Inhibition of the renin-angiotensin system attenuates the development of liver fibrosis and oxidative stress in rats. Clin Exp Pharmacol Physiol 35 2 (2008) 159-167
147. Fabris C., Toniutto P., Bitetto D., et al. Sex-related influence of angiotensin-converting enzyme polymorphisms on fibrosis progression due to recurrent hepatitis C after liver transplantation. J Gastroenterol 42 7 (2007) 543-549
148. Ibanez P., Solis N., Pizarro M., et al. Effect of losartan on early liver fibrosis development in a rat model of nonalcoholic steatohepatitis. J Gastroenterol Hepatol 22 6 (2007) 846-851
149. Kurikawa N., Suga M., Kuroda S., et al. An angiotensin II type 1 receptor antagonist, olmesartan medoxomil, improves experimental liver fibrosis by suppression of proliferation and collagen synthesis in activated hepatic stellate cells. Br J Pharmacol 139 6 (2003) 1085-1094
150. Nabeshima Y., Tazuma S., Kanno K., et al. Anti-fibrogenic function of angiotensin II type 2 receptor in CCl4-induced liver fibrosis. Biochem Biophys Res Commun 346 3 (2006) 658-664
151. Ohishi T., Saito H., Tsusaka K., et al. Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats. Hepatol Res 21 2 (2001) 147-158
152. Paizis G., Gilbert R.E., Cooper M.E., et al. Effect of angiotensin II type 1 receptor blockade on experimental hepatic fibrogenesis. J Hepatol 35 3 (2001) 376-385
153. Ramos S.G., Montenegro A.P., Goissis G., et al. Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum-induced rat liver fibrosis. Pathol Int 44 9 (1994) 655-661
154. Tuncer I., Ozbek H., Ugras S., et al. Anti-fibrogenic effects of captopril and candesartan cilexetil on the hepatic fibrosis development in rat. The effect of AT1-R blocker on the hepatic fibrosis. Exp Toxicol Pathol 55 2-3 (2003) 159-166
155. Turkay C., Yonem O., Arici S., et al. Effect of angiotensin-converting enzyme inhibition on experimental hepatic fibrogenesis. Dig Dis Sci 53 3 (2008) 789-793
156. Wei H.S., Lu H.M., Li D.G., et al. The regulatory role of AT 1 receptor on activated HSCs in hepatic fibrogenesis:effects of RAS inhibitors on hepatic fibrosis induced by CCl(4). World J Gastroenterol 6 6 (2000) 824-828
157. Xiao F., Wei H., Song S., et al. Polymorphisms in the promoter region of the angiotensinogen gene are associated with liver cirrhosis in patients with chronic hepatitis B. J Gastroenterol Hepatol 21 9 (2006) 1488-1491
158. Xu W., Song S., Huang Y., et al. Effects of perindopril and valsartan on expression of transforming growth factor-beta-Smads in experimental hepatic fibrosis in rats. J Gastroenterol Hepatol 21 8 (2006) 1250-1256
159. Yoshiji H., Kuriyama S., Yoshii J., et al. Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats. Hepatology 34 4 Pt 1 (2001) 745-750
160. Yoshiji H., Yoshii J., Ikenaka Y., et al. Inhibition of renin-angiotensin system attenuates liver enzyme-altered preneoplastic lesions and fibrosis development in rats. J Hepatol 37 1 (2002) 22-30
161. Yoshiji H., Kuriyama S., Noguchi R., et al. Angiotensin-II and vascular endothelial growth factor interaction plays an important role in rat liver fibrosis development. Hepatol Res 36 2 (2006) 124-129
162. Gaedeke J., Peters H., Noble N.A., et al. TGF-beta and renal fibrosis. Contrib Nephrol 135 (2001) 153-160
163. Shimizu S., Satomura K., Aramaki T., et al. Hepatic chymase level in chronic hepatitis: co-localization of chymase with fibrosis. Hepatol Res 27 1 (2003) 62-66
164. Dixon J.B., Bhathal P.S., Jonsson J.R., et al. Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely obese. J Hepatol 39 6 (2003) 967-971
165. Powell E.E., Edwards-Smith C.J., Hay J.L., et al. Host genetic factors influence disease progression in chronic hepatitis C. Hepatology 31 4 (2000) 828-833
166. Terui Y., Saito T., Watanabe H., et al. Effect of angiotensin receptor antagonist on liver fibrosis in early stages of chronic hepatitis C. Hepatology 36 4 Pt 1 (2002) 1022
167. Yokohama S., Yoneda M., Haneda M., et al. Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis. Hepatology 40 5 (2004) 1222-1225
168. Yoshiji H., Noguchi R., Kojima H., et al. Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C. World J Gastroenterol 12 42 (2006) 6786-6791
169. Rimola A., Londono M.C., Guevara G., et al. Beneficial effect of angiotensin-blocking agents on graft fibrosis in hepatitis C recurrence after liver transplantation. Transplantation 78 5 (2004) 686-691
170. Zekry A., Whiting P., Crawford D.H., et al. Liver transplantation for HCV-associated liver cirrhosis: predictors of outcomes in a population with significant genotype 3 and 4 distribution. Liver Transpl 9 4 (2003) 339-347
171. Schiffrin E.L. Vascular and cardiac benefits of angiotensin receptor blockers. Am J Med 113 5 (2002) 409-418
172. Bosch X. Losartan-induced hepatotoxicity. JAMA 278 19 (1997) 1572
173. Yoshiji H., Kuriyama S., Yoshii J., et al. Angiotensin-II induces the tissue inhibitor of metalloproteinases-1 through the protein kinase-C signaling pathway in rat liver fibrosis development. Hepatol Res 27 1 (2003) 51-56
174. Li X., Meng Y., Yang X.S., et al. ACEI attenuates the progression of CCl4-induced rat hepatic fibrogenesis by inhibiting TGF-beta1, PDGF-BB, NF-kappaB and MMP-2,9. World J Gastroenterol 11 31 (2005) 4807-4811
175. Ueki M., Koda M., Yamamoto S., et al. Preventive and therapeutic effects of angiotensin II type 1 receptor blocker on hepatic fibrosis induced by bile duct ligation in rats. J Gastroenterol 41 10 (2006) 996-1004
176. Yoshiji H., Kuriyama S., Noguchi R., et al. Amelioration of liver fibrogenesis by dual inhibition of PDGF and TGF-beta with a combination of imatinib mesylate and ACE inhibitor in rats. Int J Mol Med 17 5 (2006) 899-904