Title: Transforming growth factor beta-1 signalling in canine hepatic diseases: new models for human fibrotic liver pathologies
Authors: Spee, Bart ×
Arends, Brigitte
van den Ingh, Ted S G A M
Brinkhof, Bas
Nederbragt, Hubertus
Ijzer, Jooske
Roskams, Tania
Penning, Louis C
Rothuizen, Jan #
Issue Date: Aug-2006
Series Title: Liver international : official journal of the International Association for the Study of the Liver vol:26 issue:6 pages:716-25
Abstract: BACKGROUND/AIMS: The purpose of this study was to validate spontaneous chronic hepatitis and cirrhosis in dogs as a potential large animal model for fibrotic liver disease in humans by evaluating their molecular pathophysiology. METHODS: Transforming growth factor-beta1 (TGF-beta1) signalling was analysed in liver samples of dogs with acute hepatitis (AH), chronic hepatitis (CH), cirrhosis (CIRR), and a specific form of cirrhosis, lobular dissecting hepatitis (LDH), in comparison with human cirrhotic samples from alcohol abuse (ALC) and hepatitis C (HC). RESULTS: Canine samples were investigated with quantitative real-time PCR (Q-PCR) and Western blotting on TGF-beta1 signalling including Smad2/3 phosphorylation. Immunohistochemistry on collagens I and III was performed. Q-PCR showed an increase in TGF-beta1 levels and downstream effector gene products in CH, LDH, and CIRR. The same fibrotic diseases also showed an increase in phosphorylated Smad2/3 and a higher deposition of collagens I and III. In contrast, in AH neither active TGF-beta1 signalling nor collagen deposition was observed. Western blot analysis on human ALC and HC indicated a high similarity with canine samples in TGF-beta1 expression and Smad2/3 phosphorylation. CONCLUSIONS: Our results demonstrate that fibrosis in spontaneous dog liver diseases is highly comparable to their human counterparts and might serve as models for anti-fibrotic strategies.
ISSN: 1478-3223
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
× corresponding author
# (joint) last author

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