Document Detail


Pomalidomide is effective for prevention and treatment of experimental skin fibrosis.
MedLine Citation:
PMID:  22904257     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Tissue 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.
METHODS: We 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.
RESULTS: Treatment 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.
CONCLUSIONS: We 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.
Authors:
Simon Weingärtner; Pawel Zerr; Michal Tomcik; Katrin Palumbo-Zerr; Alfiya Distler; Clara Dees; Christian Beyer; Sai L Shankar; Dorota Cedzik; Peter H Schafer; Oliver Distler; Georg Schett; Jörg H W Distler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-17
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  71     ISSN:  1468-2060     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-08     Completed Date:  2012-12-20     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1895-9     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Fibrosis / chemically induced,  pathology,  prevention & control*
Hydroxyproline / metabolism
Immunosuppressive Agents / pharmacology*
Mice
Mice, Inbred DBA
Mice, Mutant Strains
Myofibroblasts / drug effects,  metabolism,  pathology
Skin / drug effects,  metabolism
Skin Diseases / chemically induced,  drug therapy*,  pathology
Thalidomide / analogs & derivatives*,  pharmacology
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 50-35-1/Thalidomide; 51-35-4/Hydroxyproline; D2UX06XLB5/pomalidomide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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