Inactivation of evenness interrupted (EVI) reduces experimental fibrosis by combined inhibition of canonical and non-canonical Wnt signalling

Distler A, Ziemer C, Beyer C, Lin NY, Chen CW, Palumbo-Zerr K, Dees C, Weidemann A, Distler O, Schett G, Distler J (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

Book Volume: 73

Pages Range: 624-7

Journal Issue: 3

DOI: 10.1136/annrheumdis-2013-203995

Abstract

Canonical as well as non-canonical Wnt signalling pathways have emerged as core pathways of fibrosis. Their profibrotic effects are mediated via distinct intracellular cascades independently of each other. Thus, inhibition of both pathways may have additive antifibrotic effects. Here, we knocked down evenness interrupted (EVI) to simultaneously target for the first time canonical and non-canonical Wnt signalling in experimental fibrosis.The antifibrotic effects of siRNA-mediated knockdown of EVI were evaluated in the mouse models of bleomycin-induced skin fibrosis and in fibrosis induced by adenoviral overexpression of a constitutively active TGF-? receptor I (AdTBRI).Knockdown of EVI decreased the release of canonical and non-canonical Wnt ligands by fibroblasts and reduced the activation of canonical and non-canonical Wnt cascades in experimental fibrosis with decreased accumulation of ?-catenin and phosphorylated JNK and cJun. Inactivation of EVI exerted potent antifibrotic effects and reduced dermal thickening, myofibroblast differentiation and accumulation of collagen in the mouse models of bleomycin-induced and AdTBR-induced fibrosis.Inhibition of Wnt secretion by knockdown of EVI inhibits canonical and non-canonical Wnt signalling and effectively reduces experimental fibrosis in different preclinical models. Inhibition of Wnt secretion may thus be an interesting approach for the treatment of fibrosis.

Authors with CRIS profile

Christian Beyer Department of Medicine 3 – Rheumatology and Immunology Neng-Yu Lin Lehrstuhl für Tierphysiologie Chih-Wei Chen Naturwissenschaftliche Fakultät Katrin Palumbo-Zerr Professur für Mikrobiologie Clara Dees Department of Medicine 3 – Rheumatology and Immunology Alexander Weidemann Department of Medicine 4 – Nephrology and Hypertension Georg Schett Lehrstuhl für Innere Medizin III Jörg Distler Professur für Molekulare Mechanismen der Organfibrose

Involved external institutions

Universitätsspital Zürich (USZ) CH Switzerland (CH)

How to cite

APA:

Distler, A., Ziemer, C., Beyer, C., Lin, N.-Y., Chen, C.-W., Palumbo-Zerr, K.,... Distler, J. (2014). Inactivation of evenness interrupted (EVI) reduces experimental fibrosis by combined inhibition of canonical and non-canonical Wnt signalling. Annals of the Rheumatic Diseases, 73(3), 624-7. https://doi.org/10.1136/annrheumdis-2013-203995

MLA:

Distler, Alfiya, et al. "Inactivation of evenness interrupted (EVI) reduces experimental fibrosis by combined inhibition of canonical and non-canonical Wnt signalling." Annals of the Rheumatic Diseases 73.3 (2014): 624-7.

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