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Journal
2012 | 7 | 5 | 599-603
Article title

Macrophages, TGF-β1 expression and iron deposition in development of NASH

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EN
Abstracts
EN
A wide range of molecular markers and different types of cells in liver are possible factors for progression of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) development of liver fibrosis. We investigated biopsies from 57 patients with NASH. The material was obtained from livers and was proceed immunohistochemistry antibodies against CD68 and TGF-beta 1. In addition, biopsies were evaluated for iron content. Macrophages/-positive/could be found in all 57 cases. The number of macrophages in the sinusoids correlated with the degree of portal fibrosis:64.% of the patients with mild or intensive fibrosis had high infiltration with CD68-positive cells, while 100% of the patients without fibrosis hadlow infiltration (χ2=8.56; p=0.003). In specimens we, 69.% of patients with different degree of fibrosis expressed TGF-β1 in their portal tracts, and 100% of patients without fibrosis did demonstrate expression of the protein (χ2=23.7; p<0.001). Hepatic iron was found in 100% (9) of patients with intensive fibrosis vs. 10.3% of the patients mild fibrosis (χ2=23.4; p<0.001). Our results suggest that the macrophages and macrophage-derived TGF-beta1 are the major factors responsible for development of fibrosis and progression of chronic liver disease.
Keywords
EN
NASH   CD68   TGF-beta1   Iron  
Publisher
Journal
Year
Volume
7
Issue
5
Pages
599-603
Physical description
Dates
published
1 - 10 - 2012
online
28 - 7 - 2012
References
  • [1] Bugianesi E., McCullough A.J., Marchesini G. Insulin resistance: A metabolic pathway to chronic liver disease. Hepatology 2005; 42(5):987–1000 http://dx.doi.org/10.1002/hep.20920[Crossref]
  • [2] Willner I.R., Waters B., Patil S.R., Reuben A., Morelli J., Riely C.A. Ninety patients with nonalcoholic steatohepatitis: Insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 2001; 96(10):2957–2961 http://dx.doi.org/10.1111/j.1572-0241.2001.04667.x[Crossref]
  • [3] Marchesini G., Brizi M., Morselli-Labate A.M., Bianchi G., Bugianesi E., et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107(5):450–455. Hui JM, Hodge A, Farrell GC, Kench JG, Kriketos A, George J. Beyond insulin resistance in NASH: TNF-a or adiponectin? Hepatology 2004; 40(1):46–54 http://dx.doi.org/10.1016/S0002-9343(99)00271-5[Crossref]
  • [4] Moirand R., Mortaji A.M., Loréal O., Paillard F., Brissot P., Deugnier Y. A new syndrome of liver iron overload with normal transferrin saturation. Lancet 1997; 349:95–97 http://dx.doi.org/10.1016/S0140-6736(96)06034-5[Crossref]
  • [5] Moirand R., Jouanolle A.M., Brissot P., Le Gall J.Y., David V., Deugnier Y. Phenotypic expression of HFE mutations: A French study of 1110 unrelated iron-overloaded patients and relatives. Gastroenterology 1999; 116(2):372–377 http://dx.doi.org/10.1016/S0016-5085(99)70134-4[Crossref]
  • [6] Nelson J.E., Bhattacharya R., Lindor K.D., et al. HFE C282Y mutations are associated with advanced hepatic fibrosis in Caucasians with nonalcoholic steatohepatitis. Hepatology 2007; 46: 723–729 http://dx.doi.org/10.1002/hep.21742[Crossref]
  • [7] Bissell D.M., Roulot D., George J. Transforming growth factor-b and the liver. Hepatology 2001; 34: 859–867 http://dx.doi.org/10.1053/jhep.2001.28457[Crossref]
  • [8] Jonsson J.R., Clouston A.D., Ando Y., Kelemen L.I., Horn M.J., et al. Angiotensin-converting enzyme inhibition attenuates the progression of rat hepatic fibrosis. Gastroenterology 2001; 121: 148–155 http://dx.doi.org/10.1053/gast.2001.25480[Crossref]
  • [9] Kleiner D.E., Brunt E.M., Van Natta M., Behling C., Contos M.J., et al. Nonalcoholic Steatohepatitis Clinical Research Network: Nonalcoholic Steatohepatitis Clinical Research Network Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005, 41:1313–1321 http://dx.doi.org/10.1002/hep.20701[Crossref]
  • [10] Bissell D.M., Wang S.S., Jarnagin W.R., Roll F.J. Cell specific expression of transforming growth factor-beta in rat liver. Evidence for autocrine of hepatocyte proliferation. J Clin Invest 1995; 96: 447–455 [Crossref]
  • [11] Bissell D.M., Roulot D., George J. Transforming growth factor-b and the liver. Hepatology 2001; 34: 859–867 http://dx.doi.org/10.1053/jhep.2001.28457[Crossref]
  • [12] Gressner A.M., Weiskirchen R., Breitkopf K., Dooley S. Roles of TGF-b in hepatic fibrosis. Front Biosci 2002; 7: d793–807 http://dx.doi.org/10.2741/gressner[Crossref]
  • [13] Pietrangelo A. Hemochromatosis gene modifies course of hepatitis C viral infection. Gastroenterology 2003;124:1509–1523 http://dx.doi.org/10.1016/S0016-5085(03)00275-0[Crossref]
  • [14] Videla L.A., Fernandez V., Tapia G., Varela P. Oxidative stress-mediated hepatotoxicity of iron and copper: role of Kupffer cells. Biometals 2003;16:103–111 http://dx.doi.org/10.1023/A:1020707811707[Crossref]
  • [15] Blendis L., Oren R., Halpern Z. NASH: can we iron out the pathogenesis? Gastroenterology 2000;118:981–983 http://dx.doi.org/10.1016/S0016-5085(00)70189-2[Crossref]
  • [16] Chitturi S., George J. Interaction of iron, insulin resistance, and nonalcoholic steatohepatitis. Curr Gastroenterol Rep 2003;5:18–25 http://dx.doi.org/10.1007/s11894-003-0005-y[Crossref]
  • [17] Kadiiska M.B., Burkitt M.J., Xiang Q.H., Mason R.P. Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation. J Clin Invest 1995;96:1653–1657 [Crossref]
  • [18] Brown K.E., Dennery P.A., Ridnour L.A., et al. Effect of iron overload and dietary fat on induces of oxidative stress and hepatic fibrogenesis in rats. Liver Int 2003;23:232–234 http://dx.doi.org/10.1034/j.1600-0676.2003.00832.x[Crossref]
  • [19] Cornejo P., Varela P., Videla L.A., Fernandez V. Chronic iron overload enhances inducible nitric oxide synthase expression in rat liver. Nitric Oxide 2005;13:54–61 http://dx.doi.org/10.1016/j.niox.2005.04.009[Crossref]
  • [20] Sorrentino P., D’Angelo S., Ferbo U., Micheli P., Bracigliano A., et al. Liver iron excess in patients with hepatocellular carcinoma developed on non-alcoholic steato-hepatitis. J Hepatol 2009;50:351–357 http://dx.doi.org/10.1016/j.jhep.2008.09.011[Crossref]
  • [21] Bacon B.R., Farahvash M.J., Janney C.G., et al. Nonalcoholic steatohepatitis: an expanded clinical entity. Gastroenterology 1994; 107: 1103–1109
  • [22] Angulo P., Keach J.C., Batts K.P., et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356–1362 http://dx.doi.org/10.1002/hep.510300604[Crossref]
  • [23] Chitturi S., Weltman M., Farrell G.C., et al. HFE mutations, hepatic iron, and fibrosis: ethnic-specific association of NASH with C282Y but not with fibrotic severity. Hepatology 2002; 36:142–149 http://dx.doi.org/10.1053/jhep.2002.33892[Crossref]
Document Type
Publication order reference
YADDA identifier
bwmeta1.element.-psjd-doi-10_2478_s11536-012-0033-9
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