| Laminin-111 protein therapy prevents muscle disease in the mdx mouse model for Duchenne muscular dystrophy. | |
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MedLine Citation:
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PMID: 19416897 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Duchenne muscular dystrophy (DMD) is a devastating neuromuscular disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin results in reduced sarcolemmal integrity and increased susceptibility to muscle damage. The alpha(7)beta(1)-integrin is a laminin-binding protein up-regulated in the skeletal muscle of DMD patients and in the mdx mouse model. Transgenic overexpression of the alpha(7)-integrin alleviates muscle disease in dystrophic mice, making this gene a target for pharmacological intervention. Studies suggest laminin may regulate alpha(7)-integrin expression. To test this hypothesis, mouse and human myoblasts were treated with laminin and assayed for alpha(7)-integrin expression. We show that laminin-111 (alpha(1), beta(1), gamma(1)), which is expressed during embryonic development but absent in normal or dystrophic skeletal muscle, increased alpha(7)-integrin expression in mouse and DMD patient myoblasts. Injection of laminin-111 protein into the mdx mouse model of DMD increased expression of alpha(7)-integrin, stabilized the sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscle from exercised-induced damage. These findings demonstrate that laminin-111 is a highly potent therapeutic agent for the mdx mouse model of DMD and represents a paradigm for the systemic delivery of extracellular matrix proteins as therapies for genetic diseases. |
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Authors:
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Jachinta E Rooney; Praveen B Gurpur; Dean J Burkin |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2009-04-28 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-13 Completed Date: 2009-06-22 Revised Date: 2010-09-27 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 7991-6 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD / genetics*, metabolism Cell Separation Creatine Kinase / blood Extracellular Matrix / metabolism Humans Integrin alpha Chains / genetics*, metabolism Laminin / genetics*, metabolism, physiology* Mice Mice, Inbred C57BL Mice, Inbred mdx Mice, Transgenic Models, Biological Muscles / metabolism Muscular Dystrophy, Duchenne / genetics*, metabolism Promoter Regions, Genetic |
| Grant Support | |
ID/Acronym/Agency:
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R01AR053697/AR/NIAMS NIH HHS; R21NS058429/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Integrin alpha Chains; 0/Laminin; 0/integrin alpha7; EC 2.7.3.2/Creatine Kinase |
| Comments/Corrections | |
Erratum In:
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Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15514 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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