| Fibroblasts from the muscles of Duchenne muscular dystrophy patients are resistant to cell detachment apoptosis. | |
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MedLine Citation:
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PMID: 21851816 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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S Zanotti; S Gibertini; C Bragato; R Mantegazza; L Morandi; M Mora |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-9 |
Journal Detail:
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Title: Experimental cell research Volume: - ISSN: 1090-2422 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011. Published by Elsevier Inc. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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