Increased ΤGF-β3 in primary biliary cirrhosis: an abnormality related to pathogenesis?
OBJECTIVE
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.


CONCLUSIONS
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.
University Hospital Department of Gastroenterology, University of Crete, Faculty of Medicine, Heraklion GR-71100, Crete, Greece.
Argyro
A
Voumvouraki
Mairi
M
Koulentaki
Maria
M
Tzardi
Ourania
O
Sfakianaki
Penelope
P
Manousou
George
G
Notas
Elias
E
Kouroumalis
D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D016022:Case-Control Studies; D019698:Hepatitis C, Chronic / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000821:virology; D008105:Liver Cirrhosis, Biliary / Q000209:etiology* / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053781:Transforming Growth Factor beta2 / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism*
D015415:Biomarkers; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3