Fibrosis in the GI tract: Pathophysiology, diagnosis and treatment options

Frontiers of Gastrointestinal Research

Volumn 26, Issue , 2010, Pages 15-31

  Pinzani, Massimo ^a  

^a Dipartimento di Medicina Interna   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTIVE IMMUNITY; ANGIOGENESIS; CYSTIC FIBROSIS; FIBROBLAST; FIBROGENESIS; FIBROSIS; INFLAMMATION; INNATE IMMUNITY; INTESTINAL FIBROSIS; LIVER FIBROSIS; MESENCHYME CELL; MYOFIBROBLAST; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; STELLATE CELL; TISSUE REGENERATION; WOUND HEALING;

EID: 77949393730     PISSN: 03020665     EISSN: None     Source Type: Book Series    
DOI: 10.1159/000258275     Document Type: Review

References (92)

1. Wynn TA: Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 2007;117:524-529.
2. Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA: Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002;3:349-363.
3. Kumar V, Abbas AK, Fausto N: Tissue renewal and repair: regeneration, healing, and fibrosis; in Kumar V, Abbas AK, Fausto N (eds): Pathologic Basis of Disease. Philadelphia, Elsevier Saunders, 2005, pp 87-118.
4. Kalluri R, Neilson EG: Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest 2003;112:1776-1784.
5. Willis BC, du Bois RM, Borok Z: Epithelial origin of myofibroblasts during fibrosis in the lung. Proc Am Thorac Soc 2006;3:377-382.
6. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, et al: Endothelialto- mesenchymal transition contributes to cardiac fibrosis. Nat Med 2007;13:952-961.
7. Bucala R, Spiegel LA, Chesney J, Hogan M, Cerami A: Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1994;1:71-81.
8. Quan TE, Cowper SE, Bucala R: The role of circulating fibrocytes in fibrosis. Curr Rheumatol Rep 2006;8:145-150.
9. Brittan M, Hunt T, Jeffery R, Poulsom R, Forbes SJ, Hodivala-Dilke K, et al: Bone marrow derivation of pericryptal myofibroblasts in the mouse and human small intestine and colon. Gut 2002;50:752-757.
10. Russo FP, Alison MR, Bigger BW, Amofah E, Florou A, Amin F, et al: The bone marrow functionally contributes to liver fibrosis. Gastroenterology 2006; 130:1807-1821.
11. Wake K: Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol 1980;66:303-353.
12. Geerts A: On the origin of stellate cells: mesodermal, endodermal or neuro-ectodermal? J Hepatol 2004;40:331-334.
13. Kiassov AP, Van Eyken P, van Pelt JF, Depla E, Fevery J, Desmet VJ, Yap SH: Desmin expressing nonhematopoietic liver cells during rat liver development: an immunohistochemical and morphometric study. Differentiation 1995;59:253-258.
14. Baba S, Fujii H, Hirose T, Yasuchika K, Azuma H, Hoppo T, et al: Commitment of bone marrow cells to hepatic stellate cells in mouse. J Hepatol 2004; 40:255-260.
15. Suskind DL, Muench MO: Searching for common stem cells of the hepatic and hematopoietic systems in the human fetal liver: CD34+ cytokeratin 7/8+ cells express markers for stellate cells. J Hepatol 2004;40:261-268.
16. Schuppan D, Ruehl M, Somasundaram R, Hahn EG: Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis 2001;21:351-372.
17. Pinzani M, Rombouts K: Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 2004;36:231-242.
18. Friedman SL: Mechanisms of hepatic fibrogenesis. Gastroenterology 2008;134:1655-1669.
19. Wynn TA: Cellular and molecular mechanisms of fibrosis. J Pathol 2008;214:199-210.
20. Calvaruso V, Maimone S, Gatt A, Tuddenham E, Thursz M, Pinzani M, Burroughs AK: Coagulation and fibrosis in chronic liver disease. Gut 2008;57: 1722-1727.
21. Bataller R, Schwabe RF, Choi YH, Yang L, Paik YH, Lindquist J, et al: NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. J Clin Invest 2003;112:1383-1394.
22. Oakley F, Teoh V, Ching-A-Sue G, Bataller R, Colmenero J, Jonsson JR, Eliopoulos AG, Watson MR, Manas D, Mann DA: Angiotensin II activates IkappaB kinase phosphorylation of RelA at Ser(536) to promote myofibroblast survival and liver fibrosis. Gastroenterology 2009;136:2334-2344.
23. Pinzani M: Unraveling the spider web of hepatic stellate cell apoptosis. Gastroenterology 2009;136: 2061-2063.
24. Novo E, Marra F, Zamara E, Valfre di Bonzo L, Monitillo L, Cannito S, Petrai I, Mazzocca A, Bonacchi A, De Franco RS, Colombatto S, Autelli R, Pinzani M, Parola M: Overexpression of Bcl-2 by activated human hepatic stellate cells: resistance to apoptosis as a mechanism of progressive hepatic fibrogenesis in humans. Gut 2006;55:1174-1182.
25. Arseneau KO, Tamagawa H, Pizarro TT, Cominelli F: Innate and adaptive immune responses related to IBD pathogenesis. Curr Gastroenterol Rep 2007;9: 508-512.
26. Meneghin MD, Hogaboam C: Infectious disease, the innate immune response, and fibrosis. J Clin Invest 2007;117:530-538.
27. Akira S, Takeda K: Toll-like receptor signalling. Nat Rev Immunol 2004;4:499-511.
28. Otte JM, Rosenberg IM, Podolsky DK: Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 2003;124:1866-1878.
29. Coelho AL, Hogaboam CM, Kunkel SL: Chemokines provide the sustained inflammatory bridge between innate and acquired immunity. Cytokine Growth Factor Rev 2005;16:553-560.
30. Brun P, Castagliuolo I, Pinzani M, Palu G, Martines D: Exposure to bacterial cell wall products triggers an inflammatory phenotype in hepatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2005;289: G571-G578.
31. Brun P, Castagliuolo I, Di Leo V, Buda A, Pinzani M, Palu' G, Martines D: Increased intestinal permeability in obese mice: new evidence in the pathogenesis of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2007;292:G518-G525.
32. Seki E, Brenner DA: Toll-like receptors and adaptor molecules in liver disease: update. Hepatology 2008; 48:322-335.
33. Wynn TA, Cheever AW, Jankovic D, Poindexter RW, Caspar P, Lewis FA, et al: An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature 1995;376:594-596.
34. Cheever AW, Williams ME, Wynn TA, Finkelman FD, Seder RA, Cox TM, et al: Anti-IL-4 treatment of Schistosoma mansoni infected mice inhibits development of T cells and non-B, non-T cells expressing Th2 cytokines while decreasing egg-induced hepatic fibrosis. J Immunol 1994;153:753-759.
35. Chiaramonte MG, Donaldson DD, Cheever AW, Wynn TA: An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J Clin Invest 1999;104:777-785.
36. Pesce J, Kaviratne M, Ramalingam TR, Thompson RW, Urban JF Jr, Cheever AW, et al: The IL-21 receptor augments Th2 effector function and alternative macrophage activation. J Clin Invest 2006;116:2044-2055.
37. Reiman RM, Thompson RW, Feng CG, Hari D, Knight R, Cheever AW, et al: Interleukin-5 (IL-5) augments the progression of liver fibrosis by regulating IL-13 activity. Infect Immun 2006;74:1471-1479.
38. Hoffmann KF, McCarty TC, Segal DH, Chiaramonte M,Hesse M, Davis EM, et al: Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions. FASEB J 2001;15:2545-2547.
39. Sandler NG, Mentink-Kane MM, Cheever AW, Wynn TA: Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J Immunol 2003;171:3655-3667.
40. Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, et al: Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol 2001;167:6533-6544.
41. Decitre M, Gleyzal C, Raccurt M, Peyrol S, Aubert- Foucher E, Csiszar K, et al: Lysyl oxidase-like protein localizes to sites of de novo fibrinogenesis in fibrosis and in the early stromal reaction of ductal breast carcinomas. Lab Invest 1998;78:143-151.
42. Akiri G, Sabo E, Dafni H, Vadasz Z, Kartvelishvily Y, Gan N, et al: Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo. Cancer Res 2003;63:1657-1666.
43. Wang S, Hirschberg R: BMP7 antagonizes TGF?- dependent fibrogenesis in mesangial cells. Am J Physiol Renal Physiol 2003;284:F1006-F1013.
44. Cheng S, Lovett DH: Gelatinase A (MMP-2) is necessary and sufficient for renal tubular cell epithelialmesenchymal transformation. Am J Pathol 2003; 162:1937-1949.
45. Underwood DC, Osborn RR, Bochnowicz S, Webb EF, Rieman DJ, Lee JC, et al: SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol 2000;279:L895-L902.
46. Heymans S, Lupu F, Terclavers S, Vanwetswinkel B, Herbert JM, Baker A, et al: Loss or inhibition of uPA or MMP-9 attenuates LV remodelling and dysfunction after acute pressure overload in mice. Am J Pathol 2005;166:15-25.
47. Kim H, Oda T, Lopez-Guisa J, Wing D, Edwards DR, Soloway PD, et al: TIMP-1 deficiency does not attenuate interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol 2001;12:736-748.
48. Vaillant B, Chiaramonte MG, Cheever AW, Soloway PD, Wynn TA: Regulation of hepatic fibrosis and extracellular matrix genes by the Th response: new insight into the role of tissue inhibitors of matrix metalloproteinases. J Immunol 2001;167:7017-7026.
49. Fertin C, Nicolas JF, Gillery P, Kalis B, Banchereau J, Maquart FX: Interleukin-4 stimulates collagen synthesis by normal and scleroderma fibroblasts in dermal equivalents. Cell Mol Biol 1991;37:823-829.
50. Sempowski GD, Beckmann MP, Derdak S, Phipps RP: Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors: role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. J Immunol 1994;152:3606-3614.
51. Doucet C, Brouty-Boye D, Pottin-Clemenceau C, Canonica GW, Jasmin C, Azzarone B: Interleukin (IL)-4 and IL-13 act on human lung fibroblasts: implication in asthma. J Clin Invest 1998;101:2129-2139.
52. Zurawski SM, Vega F Jr, Huyghe B, Zurawski G: Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J 1993;12:2663-2670.
53. Novo E, Parola M: Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 2008;1:5.
54. Casini A, Galli A, Calabro A, Di Lollo S, Orsini B, Arganini L, Jezequel AM, Surrenti C: Ethanol-induced alterations of matrix network in the duodenal mucosa of chronic alcohol abusers. Virchows Arch 1999;434:127-135.
55. Pinzani M, Marra F: Cytokine receptors and signaling in hepatic stellate cells. Semin Liver Dis 2001; 21:397-416.
56. Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW: Insights into the pathobiology of hepatitis C virus-associated cirrhosis: analysis of intrahepatic differential gene expression. Am J Pathol 2002;160:641-654.
57. Shackel NA, McGuinness PH, Abbott CA, Gorrell MD, McCaughan GW: Identification of novel molecules and pathogenic pathways in primary biliary cirrhosis: cDNA array analysis of intrahepatic differential gene expression. Gut 2001;49:565-576.
58. Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, et al: Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology 2002;35:1010-1021.
59. DeLeve LD: Hepatic microvasculature in liver injury. Semin Liver Dis 2007;27:390-400.
60. Rosmorduc O, Wendum D, Corpechot C, Galy B, Sebbagh N, Raleigh J, et al: Hepatocellular hypoxiainduced vascular endothelial growth factor expression and angiogenesis in experimental biliary cirrhosis. Am J Pathol 1999;155:1065-1073.
61. Ankoma-Sey V, Matli M, Chang KB, Lalazar A, Donner DB, Wong L, et al: Coordinated induction of VEGF receptors in mesenchymal cell types during rat hepatic wound healing. Oncogene 1998;17: 115-121.
62. Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E, et al: Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 2005;42:1339-1348.
63. Wang YQ, Luk JM, Ikeda K, Man K, Chu AC, Kaneda K, et al: Regulatory role of vHL/HIF-1alpha in hypoxia-induced VEGF production in hepatic stellate cells. Biochem Biophys Res Commun 2004;317:358-362.
64. Novo E, Cannito S, Zamara E, Valfre di BL, Caligiuri A, Cravanzola C, et al: Proangiogenic cytokines as hypoxia-dependent factors stimulating migration of human hepatic stellate cells. Am J Pathol 2007; 170:1942-1953.
65. Nakamura T, Torimura T, Sakamoto M, Hashimoto O, Taniguchi E, Inoue K, et al: Significance and therapeutic potential of endothelial progenitor cell transplantation in a cirrhotic liver rat model. Gastroenterology 2007;133:91-107.
66. Ricard-Blum S, Bresson-Hadni S, Vuitton DA, Ville G, Grimaud JA: Hydroxypyridinium collagen crosslinks in human liver fibrosis: study of alveolar echinococcosis. Hepatology 1992;15:599-602.
67. Hayasaka A, Ilda S, Suzuki N, Kondo F, Miyazaki M, Yonemitsu H: Pyridinoline collagen cross-links in patients with chronic viral hepatitis and cirrhosis. J Hepatol 1996;24:692-698.
68. Issa R, Zhou X, Constandinou CM, Fallowfield J, Millward-Sadler H, Gaca MD, Sands E, Suliman I, Trim N, Knorr A, Arthur MJ, Benyon RC, Iredale JP: Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterology 2004;126:1795-1808.
69. Iredale JP: Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 2007;117:539-548.
70. Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S, et al: Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 2005;115:56-65.
71. Poynard T, Bedossa P, Opolon P: Natural history of liver fibrosis progression in patients with chronic hepatitis C: the OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349:825-832.
72. Pinzani M: New kids on the block: pancreatic stellate cells enter the fibrogenesis world. Gut 1999;44: 451-452.
73. Pinzani M: Pancreatic stellate cells: new kids become mature. Gut 2006;55:12-14.
74. Shimizu K: Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis. J Gastroenterol 2008;43:823-832.
75. Vonlaufen A, Wilson JS, Apte MV: Molecular mechanisms of pancreatitis: current opinion. J Gastroenterol Hepatol 2008;23:1339-1348.
76. Masamune A, Kikuta K, Satoh M, et al: Proteaseactivated receptor-2-mediated proliferation and collagen production of rat pancreatic stellate cells. J Pharmacol Exp Ther 2005;312:651-658.
77. Watanabe S, Nagashio Y, Asaumi H, Nomiyama Y, Taguchi M, Tashiro M, et al: Pressure activates rat pancreatic stellate cells. Am J Physiol Gastrointest Liver Physiol 2004;287:G1175-G1181.
78. Silverstein MD, Loftus EV, Sandborn WJ, Tremaine WJ, Feagan BG, Nietert PJ, Harmsen WS, Zinsmeister AR: Clinical course and costs of care for Crohn's disease: Markov model analysis of a population-based cohort. Gastroenterology 1999; 117:49-57.
79. Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J: Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001;49:777-782.
80. Cosnes J, Nion-Larmurier I, Beaugerie L, et al: Impact of the increasing use of immunosuppressants in Crohn's disease on the need for intestinal surgery. Gut 2005;54:237-241.
81. Rieder F, Fiocchi C: Intestinal fibrosis in IBD: a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol 2009;6:228-235.
82. Sartor RB: Microbial influences in inflammatory bowel diseases. Gastroenterology 2008;134:577-594.
83. Fiocchi C: Immune-nonimmune cell interactions: the other crosstalk between innate and adaptive immunity; in Hibi T (ed): Recent Advances in Inflammatory Bowel Disease. Tokyo, Elsevier, 2007, pp 29-35
84. Pinzani M, Vizzutti F, Arena U, Marra F: Technology insights: non invasive assessment of liver fibrosis by biochemical scores and elastography. Nat Rev Gastroenterol Hepatol 2008;5:95-106.
85. Witt H, Apte MV, Keim V, Wilson JS: Chronic pancreatitis: challenges and advances in pathogenesis, genetics, diagnosis, and therapy. Gastroenterology 2007;132:1557-1573.
86. Bozkurt T, Braun U, Leferink S, Gilly G, Lux G: Comparison of pancreatic morphology and exocrine functional impairment in patients with chronic pancreatitis. Gut 1994;35:1132-1136.
87. Abreu MT, Taylor KD, Lin YC, Hang T, Gaiennie J, Landers CJ, Vasiliauskas EA, Kam LY, Rojany M, Papadakis KA, Rotter JI, Targan SR, Yang H: Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease. Gastroenterology 2002;123:679-688.
88. Danese S, Sans M, Spencer DM, Beck I, Donate F, Plunkett ML, de la Motte C, Redline R, Shaw DE, Levine AD, Mazar AP, Fiocchi C: Angiogenesis blockade as a new therapeutic approach to experimental colitis. Gut 2007;56:855-862.
89. Pinzani M, Rombouts K, Colagrande S: Fibrosis in chronic liver diseases: diagnosis and management. J Hepatol 2005;42 (suppl 1):S22-S36.
90. Iredale JP, Benyon RC, Pickering J, McCullen M, Northrop M, Pawley S, et al: Mechanisms of spontaneous resolution of rat liver fibrosis: hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors. J Clin Invest 1998;102: 538-549.
91. Wright MC, Issa R, Smart DE, Trim N, Murray GI, Primrose JN, et al: Gliotoxin stimulates the apoptosis of human and rat hepatic stellate cells and enhances the resolution of liver fibrosis in rats. Gastroenterology 2001;121:685-698.
92. Caplan AI, Dennis JE: Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006;98:1076-1084.