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Transforming growth factor β-1 signalling in canine hepatic diseases: new models for human fibrotic liver pathologies

Authors

  • Bart Spee,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 1 Brigitte Arends,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 1 Ted S. G. A. M. Van Den Ingh,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 2 Bas Brinkhof,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 1 Hubertus Nederbragt,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 2 Jooske Ijzer,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 2 Tania Roskams,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • 3 Louis C. Penning,

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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  • and 1 Jan Rothuizen 1

    1. Departments of 1Clinical Sciences of Companion Animals2Pathobiology, Faculty of Veterinary Medicine, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands3Department of Pathology, University Hospitals of Leuven, Leuven, Belgium
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Bart Spee, Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, University Utrecht, PO Box 80.154, 3508 TD Utrecht, The Netherlands.
Tel: +31-30 2533943
Fax: +31-30 2518126
e-mail: B.Spee@vet.uu.nl

Abstract

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-β1 (TGF-β1) 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-β1 signalling including Smad2/3 phosphorylation. Immunohistochemistry on collagens I and III was performed. Q-PCR showed an increase in TGF-β1 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-β1 signalling nor collagen deposition was observed. Western blot analysis on human ALC and HC indicated a high similarity with canine samples in TGF-β1 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.

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