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MeSH Review


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Disease relevance of Fibrosis


Psychiatry related information on Fibrosis


High impact information on Fibrosis

  • Ankylosing spondylitis with fibrosis and carcinoma of the lung [12].
  • Hereditary hemochromatosis is a prevalent genetic disorder of iron hyperabsorption leading to hyperferremia, tissue iron deposition and complications including cirrhosis, hepatocarcinoma, cardiomyopathy and diabetes [13].
  • Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1) [14].
  • We describe mutations in NPHP3 in families with isolated NPHP and in families with NPHP with associated hepatic fibrosis or tapeto-retinal degeneration [15].
  • Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis [15].

Chemical compound and disease context of Fibrosis

  • Gastrointestinal bleeding after abrupt cessation of propranolol administration in cirrhosis [16].
  • Decreased serum HDL3, cholesterol levels in cirrhosis of the liver [17].
  • All patients who had received cyclosporine had interstitial fibrosis, tubular atrophy, or both [18].
  • In a study of 26 patients with cirrhosis, plasma norepinephrine concentrations were significantly higher in 19 patients who abnormally excreted an acute water load than in seven who excreted the load normally (8324 +/- 116 vs. 306 +/- 33 pg per milliliter; P less than 0.001) [19].
  • METHODS: In a double-blind, prospective trial, 199 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide (25 micrograms per hour) or placebo for five days [20].
  • In bleomycin-induced fibrosis in mice, TSA prevented dermal accumulation of extracellular matrix in vivo [21].
  • There were statistically significant but weak correlations of fibrosis with platelet count, albumin, bilirubin, INR, and hyaluronic acid; however, changes in these did not correlate with or predict changes in fibrosis in the liver biopsy [22].
  • Calcium is natriuretic in patients with preascitic cirrhosis; it also decreases norepinephrine release, which could be responsible for decreased reabsorption of sodium in the Henle's loop [23].
  • Hepatic steatosis, injury, fibrosis, markers of lipid peroxidation/oxidant stress, and systemic insulin sensitivity were evaluated [24].
  • In the model of preestablished dermal fibrosis, imatinib not only stopped further progression of fibrosis but also induced regression of preexisting dermal fibrosis, with a reduction in dermal thickness below pretreatment levels [25].
  • In a further experiment, insulin treatment protected against fibrosis and CRP increases in HFD+DM, showing that diabetes, not streptozotocin, causes the fibrosis [26].

Biological context of Fibrosis


Anatomical context of Fibrosis


Gene context of Fibrosis

  • We have previously described a mutation in the keratin 18 gene in a patient with cryptogenic cirrhosis, but the importance of mutations in the keratin 8 and keratin 18 genes in such patients is unclear [36].
  • IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis [37].
  • In response to external stress, Klf5(+/-) mice showed diminished levels of arterial-wall thickening, angiogenesis, cardiac hypertrophy and interstitial fibrosis [38].
  • In contrast, FGF-6(-/-) mutant mice show a severe regeneration defect with fibrosis and myotube degeneration [39].
  • Fibrosis increased despite the fact that IL-13 levels decreased significantly in the liver and serum [40].
  • We show that local and transient TGF-beta1 overexpression induces homogenous, prolonged, and progressive pleural fibrosis without pleurodesis, associated with severe impairment of pulmonary function [41].

Analytical, diagnostic and therapeutic context of Fibrosis


  1. Heterozygous MZ alpha 1-antitrypsin deficiency in adults with chronic active hepatitis and cryptogenic cirrhosis. Hodges, J.R., Millward-Sadler, G.H., Barbatis, C., Wright, R. N. Engl. J. Med. (1981) [Pubmed]
  2. Disruption of DAG1 in differentiated skeletal muscle reveals a role for dystroglycan in muscle regeneration. Cohn, R.D., Henry, M.D., Michele, D.E., Barresi, R., Saito, F., Moore, S.A., Flanagan, J.D., Skwarchuk, M.W., Robbins, M.E., Mendell, J.R., Williamson, R.A., Campbell, K.P. Cell (2002) [Pubmed]
  3. Risk of cirrhosis and primary liver cancer in alpha 1-antitrypsin deficiency. Eriksson, S., Carlson, J., Velez, R. N. Engl. J. Med. (1986) [Pubmed]
  4. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. Sort, P., Navasa, M., Arroyo, V., Aldeguer, X., Planas, R., Ruiz-del-Arbol, L., Castells, L., Vargas, V., Soriano, G., Guevara, M., Ginès, P., Rodés, J. N. Engl. J. Med. (1999) [Pubmed]
  5. Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding. Villanueva, C., Balanzó, J., Novella, M.T., Soriano, G., Sáinz, S., Torras, X., Cussó, X., Guarner, C., Vilardell, F. N. Engl. J. Med. (1996) [Pubmed]
  6. A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma. de Lima, V.M., Oliveira, C.P., Alves, V.A., Chammas, M.C., Oliveira, E.P., Stefano, J.T., de Mello, E.S., Cerri, G.G., Carrilho, F.J., Caldwell, S.H. J. Hepatol. (2008) [Pubmed]
  7. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Fattovich, G., Stroffolini, T., Zagni, I., Donato, F. Gastroenterology (2004) [Pubmed]
  8. Plasma amino acid abnormalities in the alcoholic: respective role of alcohol, nutrition, and liver injury. Shaw, S., Lieber, C.S. Gastroenterology (1978) [Pubmed]
  9. Abdominal tuberculosis: CT evaluation. Hulnick, D.H., Megibow, A.J., Naidich, D.P., Hilton, S., Cho, K.C., Balthazar, E.J. Radiology. (1985) [Pubmed]
  10. Clinical significance of extrapyramidal signs in patients with cirrhosis. Jover, R., Compañy, L., Gutiérrez, A., Lorente, M., Zapater, P., Poveda, M.J., Such, J., Pascual, S., Palazón, J.M., Carnicer, F., Ferrandis, F., Pérez-Mateo, M. J. Hepatol. (2005) [Pubmed]
  11. Neonatal screening for galactosemia by quantitative analysis of hexose monophosphates using tandem mass spectrometry: a retrospective study. Jensen, U.G., Brandt, N.J., Christensen, E., Skovby, F., Nørgaard-Pedersen, B., Simonsen, H. Clin. Chem. (2001) [Pubmed]
  12. Ankylosing spondylitis with fibrosis and carcinoma of the lung. Shankar, P.S. CA: a cancer journal for clinicians. (1982) [Pubmed]
  13. Constitutive hepcidin expression prevents iron overload in a mouse model of hemochromatosis. Nicolas, G., Viatte, L., Lou, D.Q., Bennoun, M., Beaumont, C., Kahn, A., Andrews, N.C., Vaulont, S. Nat. Genet. (2003) [Pubmed]
  14. Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1). Yamada, K., Andrews, C., Chan, W.M., McKeown, C.A., Magli, A., de Berardinis, T., Loewenstein, A., Lazar, M., O'Keefe, M., Letson, R., London, A., Ruttum, M., Matsumoto, N., Saito, N., Morris, L., Del Monte, M., Johnson, R.H., Uyama, E., Houtman, W.A., de Vries, B., Carlow, T.J., Hart, B.L., Krawiecki, N., Shoffner, J., Vogel, M.C., Katowitz, J., Goldstein, S.M., Levin, A.V., Sener, E.C., Ozturk, B.T., Akarsu, A.N., Brodsky, M.C., Hanisch, F., Cruse, R.P., Zubcov, A.A., Robb, R.M., Roggenkäemper, P., Gottlob, I., Kowal, L., Battu, R., Traboulsi, E.I., Franceschini, P., Newlin, A., Demer, J.L., Engle, E.C. Nat. Genet. (2003) [Pubmed]
  15. Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis. Olbrich, H., Fliegauf, M., Hoefele, J., Kispert, A., Otto, E., Volz, A., Wolf, M.T., Sasmaz, G., Trauer, U., Reinhardt, R., Sudbrak, R., Antignac, C., Gretz, N., Walz, G., Schermer, B., Benzing, T., Hildebrandt, F., Omran, H. Nat. Genet. (2003) [Pubmed]
  16. Gastrointestinal bleeding after abrupt cessation of propranolol administration in cirrhosis. Lebrec, D., Bernuau, J., Rueff, B., Benhamou, J.P. N. Engl. J. Med. (1982) [Pubmed]
  17. Decreased serum HDL3, cholesterol levels in cirrhosis of the liver. Okazaki, M., Hara, I., Tanaka, A., Kodama, T., Yokoyama, S. N. Engl. J. Med. (1981) [Pubmed]
  18. Renal histopathologic alterations in patients treated with cyclosporine for uveitis. Palestine, A.G., Austin, H.A., Balow, J.E., Antonovych, T.T., Sabnis, S.G., Preuss, H.G., Nussenblatt, R.B. N. Engl. J. Med. (1986) [Pubmed]
  19. Potential role of increased sympathetic activity in impaired sodium and water excretion in cirrhosis. Bichet, D.G., Van Putten, V.J., Schrier, R.W. N. Engl. J. Med. (1982) [Pubmed]
  20. Sclerotherapy with or without octreotide for acute variceal bleeding. Besson, I., Ingrand, P., Person, B., Boutroux, D., Heresbach, D., Bernard, P., Hochain, P., Larricq, J., Gourlaouen, A., Ribard, D. N. Engl. J. Med. (1995) [Pubmed]
  21. Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis. Huber, L.C., Distler, J.H., Moritz, F., Hemmatazad, H., Hauser, T., Michel, B.A., Gay, R.E., Matucci-Cerinic, M., Gay, S., Distler, O., Jüngel, A. Arthritis Rheum. (2007) [Pubmed]
  22. Progression of fibrosis in advanced chronic hepatitis C: evaluation by morphometric image analysis. Goodman, Z.D., Becker, R.L., Pockros, P.J., Afdhal, N.H. Hepatology (2007) [Pubmed]
  23. Natriuretic and aquaretic effects of intravenously infused calcium in preascitic human cirrhosis: physiopathological and clinical implications. Sansoè, G., Wong, F. Gut (2007) [Pubmed]
  24. Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis. Yamaguchi, K., Yang, L., McCall, S., Huang, J., Yu, X.X., Pandey, S.K., Bhanot, S., Monia, B.P., Li, Y.X., Diehl, A.M. Hepatology (2007) [Pubmed]
  25. Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis. Akhmetshina, A., Venalis, P., Dees, C., Busch, N., Zwerina, J., Schett, G., Distler, O., Distler, J.H. Arthritis Rheum. (2009) [Pubmed]
  26. Diabetes is a progression factor for hepatic fibrosis in a high fat fed mouse obesity model of non-alcoholic steatohepatitis. Lo, L., McLennan, S.V., Williams, P.F., Bonner, J., Chowdhury, S., McCaughan, G.W., Gorrell, M.D., Yue, D.K., Twigg, S.M. J. Hepatol. (2011) [Pubmed]
  27. Propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a controlled study. Lebrec, D., Poynard, T., Hillon, P., Benhamou, J.P. N. Engl. J. Med. (1981) [Pubmed]
  28. Sonic hedgehog myocardial gene therapy: tissue repair through transient reconstitution of embryonic signaling. Kusano, K.F., Pola, R., Murayama, T., Curry, C., Kawamoto, A., Iwakura, A., Shintani, S., Ii, M., Asai, J., Tkebuchava, T., Thorne, T., Takenaka, H., Aikawa, R., Goukassian, D., von Samson, P., Hamada, H., Yoon, Y.S., Silver, M., Eaton, E., Ma, H., Heyd, L., Kearney, M., Munger, W., Porter, J.A., Kishore, R., Losordo, D.W. Nat. Med. (2005) [Pubmed]
  29. Relaxin's physiological roles and other diverse actions. Sherwood, O.D. Endocr. Rev. (2004) [Pubmed]
  30. Routine pulmonary function tests during bleomycin therapy. Tests may be ineffective and potentially misleading. Lewis, B.M., Izbicki, R. JAMA (1980) [Pubmed]
  31. A novel biologic activity of thrombin: stimulation of monocyte chemotactic protein production. Grandaliano, G., Valente, A.J., Abboud, H.E. J. Exp. Med. (1994) [Pubmed]
  32. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. Castilla, A., Prieto, J., Fausto, N. N. Engl. J. Med. (1991) [Pubmed]
  33. Decreased myocardial taurine levels and hypertaurinuria in a kindred with mitral-valve prolapse and congestive cardiomyopathy. Darsee, J.R., Heymsfield, S.B. N. Engl. J. Med. (1981) [Pubmed]
  34. Chloride and potassium channels in cystic fibrosis airway epithelia. Welsh, M.J., Liedtke, C.M. Nature (1986) [Pubmed]
  35. Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Fernandez-Salguero, P., Pineau, T., Hilbert, D.M., McPhail, T., Lee, S.S., Kimura, S., Nebert, D.W., Rudikoff, S., Ward, J.M., Gonzalez, F.J. Science (1995) [Pubmed]
  36. Keratin 8 mutations in patients with cryptogenic liver disease. Ku, N.O., Gish, R., Wright, T.L., Omary, M.B. N. Engl. J. Med. (2001) [Pubmed]
  37. IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Fichtner-Feigl, S., Strober, W., Kawakami, K., Puri, R.K., Kitani, A. Nat. Med. (2006) [Pubmed]
  38. Krüppel-like zinc-finger transcription factor KLF5/BTEB2 is a target for angiotensin II signaling and an essential regulator of cardiovascular remodeling. Shindo, T., Manabe, I., Fukushima, Y., Tobe, K., Aizawa, K., Miyamoto, S., Kawai-Kowase, K., Moriyama, N., Imai, Y., Kawakami, H., Nishimatsu, H., Ishikawa, T., Suzuki, T., Morita, H., Maemura, K., Sata, M., Hirata, Y., Komukai, M., Kagechika, H., Kadowaki, T., Kurabayashi, M., Nagai, R. Nat. Med. (2002) [Pubmed]
  39. A role for FGF-6 in skeletal muscle regeneration. Floss, T., Arnold, H.H., Braun, T. Genes Dev. (1997) [Pubmed]
  40. Regulation and function of the interleukin 13 receptor alpha 2 during a T helper cell type 2-dominant immune response. Chiaramonte, M.G., Mentink-Kane, M., Jacobson, B.A., Cheever, A.W., Whitters, M.J., Goad, M.E., Wong, A., Collins, M., Donaldson, D.D., Grusby, M.J., Wynn, T.A. J. Exp. Med. (2003) [Pubmed]
  41. TGF-beta1 induces progressive pleural scarring and subpleural fibrosis. Decologne, N., Kolb, M., Margetts, P.J., Menetrier, F., Artur, Y., Garrido, C., Gauldie, J., Camus, P., Bonniaud, P. J. Immunol. (2007) [Pubmed]
  42. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. Mazzaferro, V., Regalia, E., Doci, R., Andreola, S., Pulvirenti, A., Bozzetti, F., Montalto, F., Ammatuna, M., Morabito, A., Gennari, L. N. Engl. J. Med. (1996) [Pubmed]
  43. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. Olivieri, N.F., Brittenham, G.M., McLaren, C.E., Templeton, D.M., Cameron, R.G., McClelland, R.A., Burt, A.D., Fleming, K.A. N. Engl. J. Med. (1998) [Pubmed]
  44. Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. Fan, S.T., Lo, C.M., Lai, E.C., Chu, K.M., Liu, C.L., Wong, J. N. Engl. J. Med. (1994) [Pubmed]
  45. Hepatocellular carcinoma in Italian patients with cirrhosis. Colombo, M., de Franchis, R., Del Ninno, E., Sangiovanni, A., De Fazio, C., Tommasini, M., Donato, M.F., Piva, A., Di Carlo, V., Dioguardi, N. N. Engl. J. Med. (1991) [Pubmed]
  46. NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis. Bataller, R., Schwabe, R.F., Choi, Y.H., Yang, L., Paik, Y.H., Lindquist, J., Qian, T., Schoonhoven, R., Hagedorn, C.H., Lemasters, J.J., Brenner, D.A. J. Clin. Invest. (2003) [Pubmed]
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