Original Article
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World J Gastroenterol. Oct 28, 2010; 16(40): 5057-5064
Published online Oct 28, 2010. doi: 10.3748/wjg.v16.i40.5057
Increased ΤGF-β3 in primary biliary cirrhosis: An abnormality related to pathogenesis?
Argyro Voumvouraki, Mairi Koulentaki, Maria Tzardi, Ourania Sfakianaki, Penelope Manousou, George Notas, Elias Kouroumalis
Argyro Voumvouraki, Mairi Koulentaki, Elias Kouroumalis, University Hospital Department of Gastroenterology, University of Crete, Faculty of Medicine, Heraklion GR-71100, Crete, Greece
Argyro Voumvouraki, Ourania Sfakianaki, Penelope Manousou, George Notas, Elias Kouroumalis, Liver Research Laboratory, University of Crete, Faculty of Medicine, Heraklion GR-71100, Crete, Greece
Maria Tzardi, University Hospital Department of Pathology, University of Crete, Faculty of Medicine, Heraklion GR-71100, Crete, Greece
George Notas, Laboratory of Experimental Endocrinology, University of Crete, Faculty of Medicine, Heraklion GR-71100, Crete, Greece
Author contributions: Voumvouraki A and Koulentaki M collected patient data; Tzardi M performed the pathology studies; Voumvouraki A, Sfakianaki O and Manousou P performed the measurements; Notas G and Kouroumalis E performed the statistical analysis and reviewed the manuscript; Kouroumalis E designed the research.
Supported by Research funds of the University of Crete
Correspondence to: Elias Kouroumalis, Professor, University Hospital Department of Gastroenterology, University of Crete, Faculty of Medicine, PO Box 1352, Heraklion GR-71100, Crete, Greece. kouroum@med.uoc.gr
Telephone: +30-2810-392356 Fax: +30-2810-542085
Received: June 24, 2010
Revised: July 9, 2010
Accepted: July 16, 2010
Published online: October 28, 2010
Abstract

AIM: To investigate the transforming growth factor-β (TGF-β) isoforms in the peripheral and hepatic venous blood of primary biliary cirrhosis (PBC) patients.

METHODS: We examined TGF-β1, TGF-β2 and TGF-β3 (enzyme-linked immunosorbent assay), in 27 stage IV PBC patients (27 peripheral and 15 hepatic vein sera), 35 early (I-II) PBC and 60 healthy controls. As disease controls 28 hepatitis C virus (HCV) cirrhosis (28 peripheral and 17 hepatic vein serum), 44 chronic HCV hepatitis and 38 HCV-related hepatocellular carcinomas were included. We also tested liver tissue by immunohistochemistry to identify localization of TGF isoforms.

RESULTS: TGF-β1 was significantly decreased in all cirrhotics (PBC III-IV: median 13.4 ng/mL; range, 7.4-26.2, HCV cirrhosis: 11.6 ng/mL; range, 5.0-33.8), compared to controls (30.9 ng/mL; range, 20.9-37.8). TGF-β2 was increased in viral cirrhosis but not in PBC and chronic hepatitis. TGF-β3 (47.2 pg/mL; range, 27.0-79.7 in healthy controls) was increased in early and late PBC (I-II: 94.3 pg/mL; range, 41.5-358.6; III-IV: 152.8 pg/mL; range, 60.4-361.2; P < 0.001) and decreased in viral cirrhosis (37.4 pg/mL; range, 13.3-84.0; P < 0.05). Hepatic vein TGF-β levels were analogous to those in peripheral blood. Immunohistochemistry identified all isoforms in portal tract lymphocytes, sinusoidal cells and cholangiocytes. TGF-β3 was additionally overexpressed in hepatocytes in PBC patients.

CONCLUSION: The serum profile of TGF-β isoforms is different in cirrhotics. Increased TGF-β3 is characteristic of PBC. These findings may be related to the immunological abnormalities of PBC.

Keywords: Transforming growth factor-β, Primary biliary cirrhosis, Liver fibrosis, Cirrhosis