The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin model
Open accessAbstract
Objectives There is increasing evidence that the endocannabinoid system may be involved in pathological fibrosis, and that its modulation might limit fibrotic responses. The aim of this study was to examine the capacity of a synthetic cannabinoid receptor agonist to modify skin fibrosis in the bleomycin mouse model of scleroderma.Methods Skin fibrosis was induced by local injections of bleomycin in two groups of DBA/2J mice. One group was cotreated with the synthetic cannabinoid WIN55,212-2 at 1 mg/kg/day. Skin fibrosis was evaluated by histology and skin thickness and hydroxyproline content were quantified. Markers of fibroblast activation, including α smooth muscle actin and the profibrotic cytokines transforming growth factor (TGF)β, connective tissue growth factor (CTGF) and platelet-derived growth factor (PDGF)-BB, were examined. Levels of PSMAD2/3, which are crucial in extracellular matrix overproduction, were analysed.Results Bleomycin treatment induced typical skin fibrosis. Upon WIN55,212-2 treatment dermal fibrosis was completely prevented. Subcutaneous inflammatory cell infiltration, dermal thickness and collagen content resulted similar to those of the control group. The synthetic cannabinoid prevented fibroblasts activation induced by bleomycin, paralleled by a strong inhibition of TGFβ, CTGF and PDGF-BB expression. Phosphorylation of SMAD2/3 was significantly downregulated after WIN55,212-2 exposure.Conclusions Taken together, the results indicate that the synthetic cannabinoid WIN55,212-2 is capable of preventing skin fibrosis in a mouse model of scleroderma.
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Addition of WIN55,212-2 to mice inhibits bleomycin-induced skin fibrosis by lowering fibroblast-to-myofibroblast transition and TGFβ, CTGF, and PDGF production.
“Furthermore, addition of this compound to mice inhibits bleomycin induced skin fibrosis by lowering fibroblast to myofibroblast transition and TGFβ, CTGF, and PDGF production (205).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [205]
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- Authors
- Balistreri, E., Garcia-Gonzalez, E., Selvi, E., Akhmetshina, A., Palumbo, K., Lorenzini, S., Maggio, R., Lucattelli, M., Galeazzi, M., & Distler, J. W. H.
- Affiliations
- University of Siena (IT)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Selvi, Enrico
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 70
- Issue
- 4
- Pages
- 695-699
- ISSN
- 0003-4967 (ISSN-L)
- OpenAlex
- W2118668938
- Cited by
- 56
- References
- 19
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 3 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 3 · 2014: 1 · 2013: 1 · 2012: 2
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- green
- nbn-resolving.org
- Licence
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed (publishedVersion)
- OPUS FAU (Kooperativer Bibliotheksverbund Berlin-Brandenburg (KOBV), on behalf of the Universitätsbibliothek Erlangen-Nürnberg) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- WIN 55,212-2, systemic sclerosis, skin fibrosis, bleomycin-induced fibrosis, endocannabinoid system, fibroblast activation, TGF-beta, connective tissue growth factor, PDGF-BB, Smad2/3 phosphorylation, extracellular matrix, collagen deposition, antifibrotic therapy
- MeSH terms
- Animals, Bleomycin, Dermatologic Agents, Disease Models, Animal, Drug Evaluation, Preclinical, Fibroblasts, Fibrosis, Mice, Inbred DBA, Morpholines, Naphthalenes, Platelet-Derived Growth Factor, Scleroderma, Systemic, Skin, Signal Transduction, Transforming Growth Factor beta, Benzoxazines, Mice
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