Macrophages, TGF-β1 expression and iron deposition in development of NASH
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.
KeywordsNASH CD68 TGF-beta1 Iron
Unable to display preview. Download preview PDF.
- 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):46–54PubMedCrossRefGoogle Scholar
- 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, 41:1313–1321PubMedCrossRefGoogle Scholar
- 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: 447–455Google Scholar
- 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;96:1653–1657Google Scholar