Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis

Akhmetshina A, Palumbo K, Dees C, Bergmann C, Venalis P, Zerr P, Horn A, Kireva T, Beyer C, Zwerina J, Schneider H, Sadowski A, Riener MO, Macdougald OA, Distler O, Schett G, Distler J (2012)

Publication Type: Journal article

Publication year: 2012

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 3

Article Number: 1734

DOI: 10.1038/ncomms1734

Abstract

The transforming growth factor-β (TGF-β) signalling pathway is a key mediator of fibroblast activation that drives the aberrant synthesis of extracellular matrix in fibrotic diseases. Here we demonstrate a novel link between transforming growth factor-β and the canonical Wnt pathway. TGF-β stimulates canonical Wnt signalling in a p38-dependent manner by decreasing the expression of the Wnt antagonist Dickkopf-1. Tissue samples from human fibrotic diseases show enhanced expression of Wnt proteins and decreased expression of Dickkopf-1. Activation of the canonical Wnt pathway stimulates fibroblasts in vitro and induces fibrosis in vivo. Transgenic overexpression of Dickkopf-1 ameliorates skin fibrosis induced by constitutively active TGF-β receptor type I signalling and also prevents fibrosis in other TGF-β-dependent animal models. These findings demonstrate that canonical Wnt signalling is necessary for TGF-β-mediated fibrosis and highlight a key role for the interaction of both pathways in the pathogenesis of fibrotic diseases. © 2012 Macmillan Publishers Limited. All rights reserved.

Authors with CRIS profile

Clara Dees Department of Medicine 3 – Rheumatology and Immunology Pawel Zerr Department of Medicine 3 – Rheumatology and Immunology Angelika Horn Medizinische Fakultät Christian Beyer Department of Medicine 3 – Rheumatology and Immunology Holm Schneider Professur für Kinderheilkunde/Experimentelle Perinatalmedizin Georg Schett Lehrstuhl für Innere Medizin III Jörg Distler Professur für Molekulare Mechanismen der Organfibrose

Involved external institutions

Universitätsspital Zürich (USZ) CH Switzerland (CH) University of Michigan US United States (USA) (US)

How to cite

APA:

Akhmetshina, A., Palumbo, K., Dees, C., Bergmann, C., Venalis, P., Zerr, P.,... Distler, J. (2012). Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis. Nature Communications, 3. https://doi.org/10.1038/ncomms1734

MLA:

Akhmetshina, Alfiya, et al. "Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis." Nature Communications 3 (2012).

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