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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-63271

Akhmetshina, Alfiya; Palumbo, Katrin; Dees, Clara; Bergmann, Christina; Venalis, Paulius; Zerr, Pawel; Horn, Angelika; Kireva, Trayana; Beyer, Christian; Zwerina, Jochen; Schneider, Holm; Sadowski, Anika; Riener, Marc-Oliver; MacDougald, Ormond A; Distler, Oliver; Schett, Georg; Distler, Jörg H W (2012). Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis. Nature Communications, 3:735.

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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.

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66 citations in Web of Science®
74 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
DDC:610 Medicine & health
Language:English
Date:2012
Deposited On:11 Jul 2012 07:21
Last Modified:29 Nov 2013 18:07
Publisher:Nature Publishing Group
ISSN:2041-1723
Publisher DOI:10.1038/ncomms1734
PubMed ID:22415826

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