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Updated: May 12, 2026
Modeling Paracrine Noncanonical Wnt Signaling In Vitro
Published on: December 10, 2021
Blockade of canonical Wnt signalling ameliorates experimental dermal fibrosis
Christian Beyer1, Helena Reichert, Hümeyra Akan
1Department of Internal Medicine 3, Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
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.
Insights
Pharmacological Wnt signalling inhibition using PKF118-310 and ICG-001 demonstrated antifibrotic effects in experimental skin fibrosis models. These novel therapies were well tolerated and show promise for treating fibrotic diseases.
Area of Science:
- Fibrosis research
- Pharmacology
- Dermatology
Background:
- Fibrosis presents a significant socioeconomic challenge with limited effective treatments.
- Wnt signalling is increasingly recognized for its role in fibrotic diseases like systemic sclerosis.
Purpose of the Study:
- To evaluate the potential of pharmacological Wnt signalling inhibition as an antifibrotic therapy.
- To assess the efficacy of novel Wnt inhibitors PKF118-310 and ICG-001 in experimental dermal fibrosis.
Main Methods:
- Tested PKF118-310 and ICG-001 in bleomycin-induced dermal fibrosis models (prevention and treatment).
- Evaluated antifibrotic effects in fibrosis induced by transforming growth factor (TGF)-β receptor I overexpression.
- Assessed outcomes via skin thickness, hydroxyproline content, and myofibroblast counts.
Main Results:
- PKF118-310 and ICG-001 were well tolerated in all experimental models.
- Both inhibitors demonstrated significant antifibrotic effects in bleomycin-induced fibrosis, preventing and reversing disease progression.
- The Wnt inhibitors effectively reduced fibrosis driven by TGF-β receptor I.
Conclusions:
- Inhibition of canonical Wnt signalling via PKF118-310 and ICG-001 showed consistent antifibrotic activity across various skin fibrosis models.
- These therapies were well-tolerated, suggesting a promising therapeutic avenue for fibrosis.
- Further research is warranted to confirm efficacy and tolerability for clinical application.
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