Document Detail

Fibroblasts from the muscles of Duchenne muscular dystrophy patients are resistant to cell detachment apoptosis.
MedLine Citation:
PMID:  21851816     Owner:  NLM     Status:  MEDLINE    
Extracellular matrix (ECM) proteins, including collagen and growth factors, are greatly increased in tissue fibrosis and mainly secreted by fibroblasts. We previously demonstrated that muscle-derived fibroblasts from Duchenne muscular dystrophy (DMD) patients have a profibrotic phenotype, that includes significantly reduced expression of tissue inhibitor of metalloprotease 3 (TIMP-3) compared to control. Since TIMP-3 induces apoptosis in various cell types, we hypothesized increased resistance of DMD fibroblasts to apoptosis. To address this, we evaluated apoptotic nuclei, caspase 3, caspase 3 substrate expression, and migration and adhesion properties of muscle-derived fibroblasts, after applying different apoptosis-inducing treatments. We found that DMD fibroblasts were less susceptible to cell death, more adhesive, and had greater tendency to migrate than control fibroblasts - findings further supported by alterations in FAK and ERK/MAPK expression. Resistance to apoptosis and greater adhesion are likely to contribute to muscle fibrosis so a pharmacological treatment that targets dysregulated pathways involved in cell detachment apoptosis (anoikis) may limit the progressive fibrotic remodeling characteristic of DMD.
S Zanotti; S Gibertini; C Bragato; R Mantegazza; L Morandi; M Mora
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-08-09
Journal Detail:
Title:  Experimental cell research     Volume:  317     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-13     Completed Date:  2011-12-19     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2536-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
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MeSH Terms
Cells, Cultured
Child, Preschool
Fibroblasts / pathology*
Muscle, Skeletal / pathology*
Muscular Dystrophy, Duchenne / diagnosis,  pathology*
Grant Support

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