Pomalidomide is effective for prevention and treatment of experimental skin fibrosis
| Autor: | Dorota Cedzik, Jörg H W Distler, Christian Beyer, Pawel Zerr, Simon Weingärtner, Alfiya Distler, Katrin Palumbo-Zerr, Peter H. Schafer, Clara Dees, Georg Schett, Sai L. Shankar, Oliver Distler, Michal Tomcik |
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| Přispěvatelé: | University of Zurich, Distler, Jörg H W |
| Rok vydání: | 2012 |
| Předmět: |
2745 Rheumatology
Immunology 610 Medicine & health Pharmacology Skin Diseases General Biochemistry Genetics and Molecular Biology Hydroxyproline chemistry.chemical_compound Mice Rheumatology Fibrosis 1300 General Biochemistry Genetics and Molecular Biology Medizinische Fakultät medicine Immunology and Allergy Animals ddc:610 Myofibroblasts Skin 2403 Immunology integumentary system business.industry 10051 Rheumatology Clinic and Institute of Physical Medicine medicine.disease Pomalidomide Connective tissue disease Mice Mutant Strains Thalidomide CTGF Disease Models Animal chemistry Mice Inbred DBA 2723 Immunology and Allergy business Myofibroblast Immunosuppressive Agents medicine.drug Transforming growth factor |
| Zdroj: | Annals of the rheumatic diseases. 71(11) |
| ISSN: | 1468-2060 |
| Popis: | ObjectivesTissue fibrosis is a major hallmark and a leading cause of death in systemic sclerosis (SSc). Here, we investigated the antifibrotic effects of pomalidomide, an analogue of thalidomide with potent immunomodulatory effects, in preclinical models of skin fibrosis.MethodsWe evaluated the antifibrotic effects of pomalidomide in preventive as well as therapeutic treatment regimes using bleomycin-induced dermal fibrosis as a model of early, inflammatory stages of fibrosis and the tight-skin mouse model as a model of later stages of fibrosis with endogenous activation of fibroblasts.ResultsTreatment with pomalidomide in doses from 0.3 to 30 mg/kd/day prevented skin fibrosis in Tsk-1 mice and in bleomycin-induced dermal fibrosis in a dose-dependent manner and reduced the expression of transforming growth factor (TGF) β-target genes such as PAI-1, CTGF and col 1a1. Pomalidomide was also effective in the setting of pre-established fibrosis and reduced dermal thickness, myofibroblast counts and hydroxyproline content below pretreatment levels.ConclusionsWe demonstrate for the first time that pomalidomide exerts potent antifibrotic effects in different preclinical models of skin fibrosis. These findings lend preclinical support for the clinical studies of pomalidomide in SSc. |
| Databáze: | OpenAIRE |
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