RT Journal Article
SR Electronic
T1 Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 1255
OP 1258
DO 10.1136/annrheumdis-2012-202544
VO 72
IS 7
A1 Christian Beyer
A1 Helena Reichert
A1 Hümeyra Akan
A1 Tatjana Mallano
A1 Amelie Schramm
A1 Clara Dees
A1 Katrin Palumbo-Zerr
A1 Neng Yu Lin
A1 Alfiya Distler
A1 Kolja Gelse
A1 John Varga
A1 Oliver Distler
A1 Georg Schett
A1 Jörg H W Distler
YR 2013
UL http://ard.bmj.com/content/72/7/1255.abstract
AB Background and objectives Fibrosis is a major socioeconomic burden, but effective antifibrotic therapies are not available in the clinical routine. There is growing evidence for a central role of Wnt signalling in fibrotic diseases such as systemic sclerosis, and we therefore evaluated the translational potential of pharmacological Wnt inhibition in experimental dermal fibrosis. Methods We examined the antifibrotic effects of PKF118-310 and ICG-001, two novel inhibitors of downstream canonical Wnt signalling, in the models of prevention and treatment of bleomycin-induced dermal fibrosis as well as in experimental dermal fibrosis induced by adenoviral overexpression of a constitutively active transforming growth factor (TGF)-β receptor I. Results PKF118-310 and ICG-001 were well tolerated throughout all experiments. Both therapeutic approaches showed antifibrotic effects in preventing and reversing bleomycin-induced dermal fibrosis as measured by skin thickness, hydroxyproline content and myofibroblast counts. PKF118-310 and ICG-001 were effective in inhibiting TGF-β receptor I-driven fibrosis as assessed by the same outcome measures. Conclusions Blockade of canonical Wnt signalling by PKF118-310 and ICG-001 showed antifibrotic effects in different models of skin fibrosis. Both therapies were well tolerated. Although further experimental evidence for efficacy and tolerability is necessary, inhibition of canonical Wnt signalling is a promising treatment approach for fibrosis.