Liver fibrosis: A dynamic and potentially reversible process

Histology and Histopathology

Volumn 25, Issue 8, 2010, Pages 1075-1091

  Povero, Davide ^a   Busletta, Chiara ^a   Novo, Erica ^a   Di Bonzo, Lorenzo Valfrè ^a   Cannito, Stefania ^a   Paternostro, Claudia ^a   Parola, Maurizio ^a  

^a UNIVERSITY OF TURIN   (Italy)

Author keywords

Hepatic myofibroblasts; Hepatic stellate cells; Liver cirrhosis; Liver fibrosis; Myofibroblast apoptosis

Indexed keywords

ANIMALIA; MURINAE;

ANIMAL; APOPTOSIS; CELL DEDIFFERENTIATION; EXTRACELLULAR MATRIX; FIBROSIS; HUMAN; HYPERTENSION; LIVER; LIVER CIRRHOSIS; LIVER DISEASE; METABOLISM; MOUSE; PATHOPHYSIOLOGY; PHYSIOLOGY; PORTAL HYPERTENSION; REVIEW; WOUND HEALING;

ANIMALS; APOPTOSIS; CELL DEDIFFERENTIATION; EXTRACELLULAR MATRIX; FIBROSIS; HUMANS; HYPERTENSION; HYPERTENSION, PORTAL; LIVER; LIVER CIRRHOSIS; LIVER DISEASES; MICE; WOUND HEALING;

EID: 77956924615     PISSN: 02133911     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (122)

1. Acloque H., Adams M. S., Fishwick K., Bronner-Fraser M. and Nieto M. A. (2009). Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J. Clin. Invest. 119, 1438-1449.
2. Albano E. (2006). Alcohol, oxidative stress and free radical damage. Proc. Nutr. Soc. 65, 278-290.
3. Albano E., Mottaran E., Vidali M., Reale E., Saksena S., Occhino G., Burt A. D. and Day C. P. (2007). Immune response towards lipid peroxidation products as a predictor of progression of non-alcoholic fatty liver disease to advanced fibrosis. Gut 54, 987-993.
4. Aleffi S., Petrai I., Bertolani C., Parola M., Colombatto S., Novo E., Vizzutti F., Anania F. A., Milani S., Rombouts K., Laffi G., Pinzani M. and Marra F. (2005). Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 42, 1339-1348.
5. Angulo P. (2002). Non-alcoholic fatty liver disease. N. Engl. J. Med. 346, 1221-1231.
6. Ankoma-Sey V., Matli M., Chang K. B., Lalazar A., Donner D. B., Wong L., Warren R. S. and Friedman S. L. (1998). Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 17, 115-121.
7. Ankoma-Sey V., Wang Y. and Dai Z. (2000). Hypoxic stimulation of vascular endothelial growth factor expression in activated rat hepatic stellate cells. Hepatology 31, 141-148.
8. Bataller R. and Brenner D. A. (2005). Liver fibrosis. J. Clin. Invest. 115, 109-118.
9. Bataller R., Schwabe R. F., Choi Y. H., Yang L., Paik Y. H., Lindquist J., Qian T., Schoonhoven R., Hagedorn C. H., Leemasters J. J., Brenner D. A. (2003). NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J. Clin. Invest. 112, 1383-1394.
10. Bataller R., Sancho-Bru P., Ginès P. and Brenner D. A. (2007). Liver fibrogenesis: a new role for the renin-angiotensin system. Antioxid. Redox Signal. 7, 1346-1355.
11. Baum B., Settleman J. and Quinlan M. P. (2008). Transitions between epithelial and mesenchymal states in development and disease. Sem. Cell. Dev. Biol. 19, 294-308.
12. Bozova S. and Elpek G. O. (2007). Hypoxia-inducible factor-1alpha expression in experimental cirrhosis: correlation with vascular endothelial growth factor expression and angiogenesis. APMIS 115, 795-801.
13. Cannito S., Novo E., Valfrè di Bonzo L., Busletta C., Colombatto S. and Parola M. (2009). Epithelial-mesenchymal transition: from molecular mechanisms, redox regulation to implications in human health and disease. Antioxidants Redox Signal. (In press).
14. Carmeliet P. (2003). Angiogenesis in health and disease. Nat. Med. 9, 653-660.
15. Carmeliet P. (2004). Manipulating angiogenesis in medicine. J. Intern. Med. 255, 538-561.
16. Cassiman D. and Roskams T. (2002). Beauty is in the eye of the beholder: emerging concepts and pitfalls in hepatic stellate cell research. J. Hepatol. 37, 527-535.
17. Cassiman D., Libbrecht L., Desmet V., Denef C. and Roskams T. (2002). Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J. Hepatol. 36, 200-209.
18. Chaffer C. L., Thompson E. W. and Williams E. M. (2007). Mesenchymal to epithelial transition in development and disease. Cells Tissues Organs 185, 7-19.
19. Corpechot C., Barbu V., Wendum D., Kinnman N., Rey C., Poupon R., Housset C. and Rosmorduc O. (2002). Hypoxia - induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 35, 1010-1021.
20. Debernardi-Venon W., Martini S., Biasi F., Vizio B., Termine A., Poli G., Brunello F., Alessandria C., Bonardi R., Saracco G., Rizzetto M. and Marzano A. (2007). AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers. J. Hepatol. 46, 1026-1033.
21. De Minicis S., Bataller R. and Brenner D. A. (2006). NADPH oxidase in the liver: defensive, offensive, or fibrogenic? Gastroenterology 131, 272-275.
22. Desmet V. J. and Roskams T. (2004). Cirrhosis reversal: a duel between dogma and myth. J. Hepatol. 40, 860-867.
23. Díaz R., Kim J. W., Hui J. J., Li Z., Swain G. P., Fong K. S., Csiszar K., Russo P. A., Rand E. B., Furth E. E. and Wells R. G. (2008). Evidence for the epithelial to mesenchymal transition in biliary atresia fibrosis. Hum. Pathol. 39, 102-15.
24. Dienstag J. L., Goldin R. D., Heathcote E. J., Hann H. W., Woessner M., Stephenson S. L., Gardner S., Gray D. F. and Schiff E. R. (2003). Histological outcome during long-term lamivudine therapy. Gastroenterology 124, 105-117.
25. Ding X., Saxena N. K., Lin S., Xu A., Srinivasan S. and Anania F. A. (2005). The roles of leptin and adiponectin: a novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology. Am. J. Pathol. 166, 1655-1669.
26. Dixon J. B., Bhathal P. S., Hughes N. R. and O'Brien P. E. (2004). Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss. Hepatology 39, 1647-1654.
27. Dooley S., Hamzavi J., Ciuclan L., Godoy P., Ilkavets I., Ehnert S., Ueberham E., Gebhardt R., Kanzler S., Geier A., Breitkopf K., Weng H. and Mertens PR. (2008). Hepatocyte-specific Smad7 expression attenuates TGF-beta-mediated fibrogenesis and protects against liver damage. Gastroenterology 135, 642-659.
28. Dufour J. F., DeLellis R. and Kaplan M. M. (1997). Reversibility of hepatic fibrosis in autoimmune hepatitis. Ann. Intern. Med. 127, 981-985.
29. Elsharkawy A. M., Oakley F. and Mann D. (2005). The role and regulation of hepatic stellate cells apoptosis in reversal of liver fibrosis. Apoptosis 10, 927-939.
30. Farci P., Roskams T., Chessa L., Peddis G., Mazzoleni A. P., Scioscia R., Serra G., Lai M. E., Loy M., Caruso L., Desmet V., Purcell R. H. and Balestrieri A. (2004). Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advancehepatic fibrosis. Gastroenterology 126, 1740-1749.
31. Fernández M., Semela D., Bruix J., Colle I., Pinzani M. and Bosch J. (2009). Angiogenesis in liver disease. J. Hepatol. 50, 604-260.
32. Forbes S. J., Russo F. P., Rey V., Burra P., Rugge M., Wright N. A. and Alison M. R. (2004). A significant proportion of myofibroblasts are of bone marrow origin in human liver fibrosis. Gastroenterology 126, 955-963.
33. Friedman S. L. (2000). Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem. 275, 2247-2250.
34. Friedman S. L. (2003). Liver fibrosis: from bench to bedside. J. Hepatol. 38, Suppl. 1, S38-S53.
35. Friedman S. L. (2004). Mechanisms of disease: mechanisms of hepatic fibrosis and therapeutic implications. Nat. Clin. Pract. Gastroenterol. Hepatol. 1, 98-105.
36. Friedman S. L. (2008a). Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver. Physiol. Rev. 88, 125-172.
37. Friedman S. L. (2008b). Mechanisms of hepatic fibrogenesis. Gastroenterology 134, 1655-1669.
38. Henderson N. C. and Iredale J. P. (2007). Liver fibrosis: cellular mechanisms of progression and resolution. Clinical Science 112, 265-280.
39. Higashiyama R., Moro T., Nakao S., Mikami K., Fukumitsu H., Ueda Y., Ikeda K., Adachi E., Bou-Gharios G., Okazaki I. and Inagaki Y. (2009). Negligible contribution of bone marrow-derived cells to collagen production during hepatic fibrogenesis in mice. Gastroenterology 137, 1459-1466.
40. Hui C. K., Leung N., Shek T. W., Yao H., Lee W. K., Lai J. Y., Lai S. T., Wong W. M., Lai L. S., Poon R. T., Lo C. M., Fan S. T. and Lau G. K. (2007). Sustained disease remission after spontaneous HBeAg seroconversion is associated with reduction in fibrosis progression in chronic hepatitis B Chinese patients. Hepatology 46, 690-698.
41. Ikejima K., Honda H., Yoshikawa M., Hirose M., Kitamura T., Takei Y. and Sato N. (2001). Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals. Hepatology 34, 288-297.
42. Iredale J. P. (2001). Hepatic stellate cell behaviour during resolution of liver fibrosis. Semin. Liver Dis. 21, 427-436.
43. Iredale J. P. (2007). Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organism. J. Clin. Invest. 117, 539-548.
44. Iredale J. P., Benyon R. C., Pickering J., McCullen M., Northrop M. and Pawley S. (1998). Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J. Clin. Invest. 102, 538-549.
45. Ismail M. H. and Pinzani M. (2009). Reversal of liver fibrosis. Saudi J. Gastroenterol. 15, 72-79.
46. Issa R., Williams E., Trim N., Kendall T., Arthur M. J., Reichen J., Benyon R. C. and Iredale J. P. (2001). Apoptosis of hepatic stellate cells: involvement in resolution of biliary fibrosis and regulation by soluble growth factors. Gut 48, 548-557.
47. Issa R., Zhou X., Constandinou C. M., Fallowfield J., Millward-Sadler H., Gaca M. D., Sands E., Suliman I., Trim N., Knorr A., Arthur M. J., Benyon R. C. and Iredale J. P. (2004). Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 126, 1795-1808.
48. Jackson J. R., Seed M. P., Kircher C. H., Willoughby D. A. and Winkler J. D. (1997). The codependence of angiogenesis and chronic inflammation. FASEB J. 11, 457-465.
49. Jung Y., McCall S. J., Li Y. X. and Diehl A. M. (2007). Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis. Hepatology 45, 1091-1096.
50. Kallis Y. N. and Forbes S. J. (2009). The bone marrow and liver fibrosis: friend or foe? J. Gastroenterol. 137, 1218-1221.
51. Kalluri K. and Weinberg R. A. (2009). The basics of epithelialmesenchymal transition. J. Clin. Invest. 119, 1420-1428.
52. Kallis Y. N., Alison M. R. and Forbes, S. J. (2007). Bone marrow stem cells and liver disease. Gut 56, 716-724.
53. Kendall T. J., Hennedige S., Aucott R. L., Hartland S. N., Vernon M. A., Benyon R. C. and Iredale J. P. (2009). p75 Neurotrophin receptor signaling regulates hepatic myofibroblast proliferation and apoptosis in recovery from rodent liver fibrosis. Hepatology 49, 901-910.
54. Kirby J. A., Robertson H., Marshall H. L., Rygiel K. A., Hudson M., Jones D. E. and Burt A. D. (2008). Epithelial to mesenchymal transition in primary sclerosing cholangitis. Liver Int. 28, 1176-1177.
55. Kisseleva T., Uchinami H., Feirt N., Quintana-Bustamante O., Segovia J. C., Schwabe R. F. and Brenner D. A. (2006). Bone marrow-derived fibrocytes participate in pathogenesis of liver fibrosis. J. Hepatol. 45, 429-438.
56. Kitade M., Yoshiji H., Kojima H., Ikenaka Y., Noguchi R., Kaji K., Yoshii J., Yanase K., Namisaki T., Asada K., Yamazaki M., Tsujimoto T., Akahane T., Uemura M. and Fukui H. (2006). Leptin-mediated neovascularization is a prerequisite for progression of nonalcoholic steatohepatitis in rats. Hepatology 44, 983-991.
57. Kral J. G., Thung S. N., Biron S., Hould F. S., Lebel S., Marceau S., Simard S. and Marceau P. (2004). Effects of surgical treatment of the metabolic syndrome on liver fibrosis and cirrhosis. Surgery 135, 48-58.
58. Krizhanovsky V., Yon M., Dickins R. A., Hearn S., Simon J., Miething C., Yee H., Zender L. and Lowe SW. (2008). Senescence of activated stellate cells limits liver fibrosis. Cell 134, 657-667.
59. Kweon Y. O., Goodman Z. D., Dienstag J. L., Schiff E. R., Brown N. A., Burchardt E., Schoonhoven R., Brenner D. A., Fried M. W. (2001). Decreasing fibrogenesis: an immunohistochemical study of paired liver biopsies following lamivudine therapy for chronic hepatitis B. J. Hepatol. 35, 749-755.
60. Lee J. M., Dedhar S., Kalluri R. and Thompson E. W. (2006). The epithelial - mesenchymal transition: new insights in signalling, development, and disease. J. Cell Biol. 172, 973-981.
61. Li C., Kong Y., Wang H., Wang S., Yu H., Liu X., Yang L., Jiang X., Li L. and Li L. (2009). Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis. J. Hepatol. 50, 1174-1183.
62. Marra F. and Bertolani C. (2009). Adipokines in liver diseases. Hepatology 50, 957-969.
63. Medina J., Caveda L., Sanz-Cameno P., Arroyo A. G., Martín- Vílchez S., Majano P. L., García-Buey L., Sánchez-Madrid F. and Moreno-Otero R. (2003). Hepatocyte growth factor activates endothelial proangiogenic mechanisms relevant in chronic hepatitis C-associated neoangiogenesis. J. Hepatol. 38, 660-667.
64. Medina J., Arroyo A. G., Sanchez-Madrid F. and Moreno-Otero R. (2004). Angiogenesis in chronic inflammatory liver diseases. Hepatology 39, 1185-1195.
65. Medina J., Sanz-Cameno P., García-Buey L., Martín- Vílchez S., López-Cabrera M. and Moreno-Otero R. (2005). Evidence of angiogenesis in primary biliary cirrhosis: an immunohistochemical descriptive study. J. Hepatol. 42, 124-131.
66. Mejias M., Garcia-Pras E., Tiani C., Miquel R., Bosch J. and Fernandez M. (2009). Beneficial effects of sorafenib on splanchnic, intrahepatic, and portocollateral circulations in portal hypertensive and cirrhotic rats. Hepatology 49, 1245-1256.
67. Moon J.-K., Welch T. P., Gonzalez F. J. and Copple B. L. (2009). Reduced liver fibrosis in Hypoxia-inducible Factor-1.-Deficient Mice. Am. J. Physiol. - Gastrointest. Liver Physiol. 296, 582-592.
68. Morales-Ruiz M. and Jimenez W. (2005). Neovascularization, angiogenesis, and vascular remodeling in portal hypertension. In: Portal hypertension: pathobiology, evaluation and treatment. Sanyal A. J. and Shah V. H. (eds). Humana Press. Totowa (NJ). pp 99-112.
69. Morales-Ruiz M., Tugues S., Cejudo-Martin P., Ros J., Melgar-Lesmen P., Fernandez-Llama P., Arroyo V., Rodés J. and Jiménez W. (2005). Ascites from cirrhotic patients induces angiogenesis through the phosphoinositide 3-kinase/Akt signaling pathway. J. Hepatol. 43, 85-91.
70. Moustakas A. and Heldin C. H. (2007). Signaling networks guiding epithelial - mesenchymal transitions during embryogenesis and cancer progression. Cancer Sci. 98, 1512-1520.
71. Muddu A. K., Guha I. N., Elsharkawy A. M. and Mann D. A. (2007). Resolving fibrosis in the diseased liver: translating the scientific promise to the clinic. J. Biocel. 39, 695-714.
72. Murphy F. R., Issa R., Zhou X., Ratnarajah S., Nagase H., Arthur M. J., Benyon C. and Iredale J. P. (2002). Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: implications for reversibility of liver fibrosis. J. Biol. Chem. 277, 11069-11076.
73. Novo E. and Parola M. (2008). Redox mechanisms in hepatic chronic wound healing and liver fibrogenesis. Fibrogenesis Tissue Repair 1, 5.
74. Novo E., Marra F., Zamara E., Valfrè di Bonzo L., Caligiuri A., Cannito S., Antonaci C., Colombatto S., Pinzani M. and Parola M. (2006a). Dose dependent and divergent effects of superoxide anion on cell death, proliferation and migration of activated human hepatic stellate cells. Gut 55, 90-97.
75. Novo E., Marra F., Zamara E., Valfrè di Bonzo L., Monitillo L., Cannito S., Petrai I., Mazzocca A., Bonacchi A., De Franco R. S., Colombatto S., Autelli R., Pinzani M. and Parola M. (2006b). Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut 55, 1174-1182.
76. Novo E., Cannito S., Zamara E., Valfrè di Bonzo L., Caligiuri A., Cravanzola C., Compagnone A., Colombatto S., Marra F., Pinzani M. and Parola M. (2007). Proangiogenic cytokines as hypoxiadependent factors stimulating migration of human hepatic stellate cells. Am. J. Pathol. 170, 1942-1953.
77. Novo E., Valfrè di Bonzo L., Cannito S., Colombatto S. and Parola M. (2009). Hepatic myofibroblasts: A heterogeneous population of multifunctional cells in liver fibrogenesis. Int. J. Biochem. Cell Biol. 41, 2089-2093.
78. Oakley F., Meso M., Iredale J. P., Green K., Marek C. J., Zhou X., May M. J., Millward-Sadler H., Wright M. C. and Mann D. A. (2005). Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 128, 108-120.
79. Oakley F., Teoh V., Ching-A-Sue G., Bataller R., Colmenero J., Jonsson J. R., Eliopoulos A. G., Watson M. R., Manas D. and Mann D. A. (2009). Angiotensin II activates I kappaB kinase phosphorylation of RelA at Ser 536 to promote myofibroblast survival and liver fibrosis. Gastroenterology 136, 2334-2344.
80. Olaso E., Salado C., Egilegor E., Gutierrez V., Santisteban A., Sancho-Bru P., Friedman S. L. and Vidal-Vanaclocha F. (2003). Proangiogenic role of tumor-activated hepatic stellate cells in experimental melanoma metastasis. Hepatology 37, 674-685.
81. Omenetti A., Popov Y., Jung Y., Choi S. S., Witek R. P., Yang L., Brown K. D., Schuppan D. and Diehl A. M. (2008a). The hedgehog pathway regulates remodelling responses to biliary obstruction in rats. Gut 57, 1275-1282.
82. Omenetti A., Porrello A., Jung Y., Yang L., Popov Y., Choi S. S., Witek R. P., Alpini G., Venter J., Vandongen H. M., Syn W. K., Baroni G. S., Benedetti A., Schuppan D. and Diehl A. M. (2008b). Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans. J. Clin. Invest. 118, 3331-3342.
83. Parola M. and Robino G. (2001). Oxidative stress - related molecules and liver fibrosis. J. Hepatol. 35, 297-306.
84. Parola M., Robino G., Marra F., Pinzani M., Bellomo G., Leonarduzzi G., Chiarugi P., Camandola S., Poli G., Waeg G., Gentilini P. and Dianzani M. U. (1998). HNE interacts directly with JNK isoforms in human hepatic stellate cells. J. Clin. Invest. 102, 1942-1950.
85. Parola M., Marra F. and Pinzani M. (2008). Myofibroblast - like cells and liver fibrogenesis: emerging concepts in a rapidly moving scenario. Mol. Asp. Med. 29, 58-66.
86. Patsenker E., Popov Y., Stickel F., Schneider V., Ledermann M., Sägesser H., Niedobitek G., Goodman S. L. and Schuppan D. (2009). Pharmacological inhibition of integrin alphavbeta3 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis. Hepatology. 50, 1501-1511.
87. Perez-Tamayo R. (1979). Cirrhosis of the liver: A reversible disease? Pathol. Ann. 14, 183-213.
88. Pinzani M. (2009). Unravelling the spider web of hepatic stellate cell apoptosis. Gastroenterology 136, 2061-2063.
89. Pinzani M. and Marra F. (2001). Cytokine receptor and signalling in hepatic stellate cells. Sem. Liv. Dis. 21, 397-417.
90. Pinzani M. and Rombouts K. (2004). Liver fibrosis - from the bench to clinical targets. Dig. Liver Dis. 36, 231-242.
91. Pinzani M., Romanelli R. G. and Magli S. (2001). Progression of fibrosis in chronic liver diseases - time to tally the score. J. Hepatol. 34, 764-767.
92. Popper H. and Undenfriend S. (1970). Correlation of biologic and morphologic investigations. Am. J. Med. 49, 707-721.
93. Poynard T., Bedossa P. and Opolon P. (1997). Natural history of liver fibrosis progressionin patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR and DOSVIRC groups. Lancet 349, 825-832.
94. Poynard T., McHutchison J., Manns M., Trepo C., Lindsay K., Goodman Z., Ling M. H. and Albrecht J. (2002). Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C. Gastroenterology 122, 1303-1313.
95. Robertson H., Kirby J. A., Yip W. W., Jones D. E. and Burt A. D. (2007). Biliary epithelial mesenchymal transition in posttransplantation recurrence of primary biliary cirrhosis. Hepatology 45, 977-981.
96. Robino G., Parola M., Marra F., Caligiuri A., DeFranco R. M. S., Zamara E., Bellomo G., Gentilini P., Pinzani M. and Dianzani, M. U. (2000). Interactions of 4-hydorxy-2, 3-alkenals and the platelet-derived growth factor ß-receptor. J. Biol. Chem. 275, 40561-40567.
97. Roskams T. and Desmet V. (1998). Ductular reaction and its diagnostic significance. Semin. Diagn. Pathol. 15, 259-269.
98. Rosmorduc O., Wendum D., Corpechot C., Galy B., Sebbagh N., Raleigh J., Housset C. and Poupon R. (1999). Hepatocellular hypoxia - induced vascular endothelial growth factor expression and angiogenesis in experimental biliary fibrosis. Am. J. Pathol. 155, 1065-1073.
99. Russo F. P., Alison M. R., Bigger B. W., Amofah E., Florou A., Amin. F., Bou-Gharios G., Jeffery R., Iredale J. P. and Forbes, S. J. (2006). The bone marrow functionally contributes to liver fibrosis. Gastroenterology 130, 1807-1821.
100. Rygiel K. A., Robertson H., Marshall H. L., Pekalski M., Zhao L., Booth T. A., Jones D. E., Burt A. D. and Kirby J. A. (2008). Epithelialmesenchymal transition contributes to portal tract fibrogenesis during human chronic liver disease. Lab. Invest. 88, 112-123.
101. Serpaggi J., Carnot F., Nalpas B., Canioni D., Guéchot J., Lebray P., Vallet-Pichard A., Fontaine H., Bedossa P. and Pol S. (2006). Direct and indirect evidence for the reversibility of cirrhosis. Hum. Pathol. 37, 1519-1526.
102. Shiratori Y., Imazeki F., Moriyama M., Yano M., Arakawa Y., Yokosuka O., Kuroki T., Nishiguchi S., Sata M., Yamada G., Fujiyama S., Yoshida H. and Omata M. (2000). Histologic improvement of fibrosis in patients with hepatitis C who have sustained response to interferon therapy. Ann. Intern. Med. 132, 517-524.
103. Stewart S. F., Vidali M., Day C. P., Albano E. and Jones D. E (2004). Oxidative stress as a trigger for cellular immune response in patients with alcoholic liver disease. Hepatology 39, 197-203.
104. Taura K., De Minicis S., Seki E., Hatano E., Iwaisako K., Osterreicher C. H., Kodama Y., Miura K., Ikai I., Uemoto S. and Brenner D. A. (2008). Hepatic stellate cells secrete angiopoietin 1 that induces angiogenesis in liver fibrosis. Gastroenterology 135, 1729-1738.
105. Thiery J. P. and Sleeman J. P. (2006). Complex networks orchestrate epithelial - mesenchymal transitions. Nature Rev. Mol. Cell. Biol. 7, 131-142.
106. Tilg H. and Hotamisligil G. S. (2006). Nonalcoholic fatty liver disease: cytokine-adipokine interplay and regulation of insulin resistance. Gastroenterology 131, 934-945.
107. Tugues S., Fernandez-Varo G., Muñoz-Luque J., Ros J., Arroyo V., Rodés J., Friedman S. L., Carmeliet P., Jiménez W. and Morales-Ruiz M. (2007). Antiangiogenic treatment with sunitinib ameliorates inflammatory infiltrate, fibrosis, and portal pressure in cirrhotic rats. Hepatology 46, 1919-1926.
108. Valfrè di Bonzo L., Ferrero I., Cravanzola C., Mareschi K., Rustichelli D., Novo E., Sanavio F., Cannito S., Zamara E., Bertero M., Davit A., Francica S., Novelli F., Colombatto S., Fagioli F. and Parola M. (2008). Human mesenchymal stem cells as a two-edged sword in hepatic regenerative medicine: engraftment and hepatocyte differentiation versus profibrogenic potential. Gut 57, 223-231.
109. Valfrè di Bonzo L., Novo E., Cannito S., Busletta C., Paternostro C., Povero D. and Parola M. (2009). Angiogenesis and liver fibrogenesis. Histol. Histopathol. 24, 1323-1334.
110. Wang Y. Q., Ikeda K., Ikebe T., Hirakawa K., Sowa M., Nakatani K., Kawada N. and Kaneda K. (2000). Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP-470 in rats. Hepatology 32, 980-989.
111. Wang Y. Q., Luk J. M., Ikeda K., Man K., Chu A. C., Kaneda K. and Fan S. T. (2004). Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells. Biochem Biophys Res Commun. 317, 358-362.
112. Wakim-Fleming J. and Mullen K. D. (2005). Long-term management of alcoholic liver disease. Clin. Liver. Dis. 9, 135-149.
113. Watson M. R., Wallace K., Gieling R. G., Manas D. M., Jaffray E., Hay R. T., Mann D. A. and Oakley F. (2008). NF-kappaB is a critical regulator of the survival of rodent and human hepatic myofibroblasts. J. Hepatol. 48, 589-597.
114. Witek R. P., Yang L., Liu R., Jung Y., Omenetti A., Syn W. K., Choi S. S., Cheong Y., Fearing C. M., Agboola K. M., Chen W. and Diehl A. M. (2009). Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepaticendothelial cells. Gastroenterology 136, 320-330.
115. Xia J. L., Dai C., Michalopoulos G. K. and Liu Y. (2006). Hepatocyte growth factor attenuates liver fibrosis induced by bile duct ligation. Am. J. Pathol. 168, 1500-1512.
116. Xu A., Wang Y., Keshaw H., Xu L. Y., Lam K. S. and Cooper, G. J. (2003). The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J. Clin. Invest. 112, 91-100.
117. Yoshiji H., Kuriyama S., Yoshii J., Ikenaka Y., Noguchi R., Hicklin D. J., Wu Y., Yanase K., Namisaki T., Yamazaki M., Tsujinoue H., Imazu H., Masaki T. and Fukui H. (2003). Vascular endothelial growth factor and receptor interaction is a prerequisite for murine hepatic fibrogenesis. Gut 52, 1347-1354.
118. Zamara E., Novo E., Marra F., Gentilini A., Romanelli R. G., Caligiuri A., Robino G., Tamagno E., Aragno M., Danni O., Autelli R., Colombatto S., Dianzani M. U., Pinzani M. and Parola M. (2004). 4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cells. J. Hepatol. 40, 60-68.
119. Zamara E., Novo E. and Parola M. (2006). Oxidative stress and liver fibrosis: from liver injury to modulation of cell signalling and response. In: Liver diseases. Biochemical mechanisms and new therapeutic insights. vol. 1. Ali S., Friedman S. L. and Mann D. (eds). Science Publishers. Enfield (NH, USA). pp 93-114.
120. Zeisberg M. and Neilson E. G. (2009). Biomarkers for epithelialmesenchymal transitions. J. Clin. Invest. 119, 1429-1437.
121. Zeisberg M., Yang C., Martino M., Duncan M. B., Rieder F., Tanjore H. and Kalluri R. (2007). Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition. J. Biol. Chem. 47, 282, 23337.
122. Zhan S. S., Jiang J. X., Wu J., Halsted C., Friedman S. L., Zern M. A. and Torok N. J. (2006). Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis in vivo. Hepatology 43, 435-445.