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FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

BACKGROUND: Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tiss...

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Detalles Bibliográficos
Autores principales: Eash, John, Olsen, Aaron, Breur, Gert, Gerrard, Dave, Hannon, Kevin
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1853093/
https://www.ncbi.nlm.nih.gov/pubmed/17425786
http://dx.doi.org/10.1186/1471-2474-8-32
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author Eash, John
Olsen, Aaron
Breur, Gert
Gerrard, Dave
Hannon, Kevin
author_facet Eash, John
Olsen, Aaron
Breur, Gert
Gerrard, Dave
Hannon, Kevin
author_sort Eash, John
collection PubMed
description BACKGROUND: Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs) and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined. METHODS: We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice. RESULTS: We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers. CONCLUSION: These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight.
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spelling pubmed-18530932007-04-20 FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension Eash, John Olsen, Aaron Breur, Gert Gerrard, Dave Hannon, Kevin BMC Musculoskelet Disord Research Article BACKGROUND: Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. The mechanisms by which unloading of muscle is sensed and translated into signals controlling tissue reduction remains a major question in the field of musculoskeletal research. While the fibroblast growth factors (FGFs) and their receptors are synthesized by, and intimately involved in, embryonic skeletal muscle growth and repair, their role maintaining adult muscle status has not been examined. METHODS: We examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice. RESULTS: We found skeletal muscle FGF4 and FGFR1 mRNA expression to be modified by hind limb suspension,. In addition, we found FGFR1 protein localized in muscle fibers within atrophying mouse muscle which appeared to be resistant to atrophy. Electroporation and ectopic expression of FGFR1 significantly inhibited the decrease in muscle fiber area within skeletal muscles of mice undergoing suspension induced muscle atrophy. Ectopic FGFR1 expression in muscle also significantly stimulated protein synthesis in muscle fibers, and increased protein degradation in weight bearing muscle fibers. CONCLUSION: These results support the theory that FGF signaling can play a role in regulation of postnatal skeletal muscle maintenance, and could offer potentially novel and efficient therapeutic options for attenuating muscle atrophy during aging, illness and spaceflight. BioMed Central 2007-04-10 /pmc/articles/PMC1853093/ /pubmed/17425786 http://dx.doi.org/10.1186/1471-2474-8-32 Text en Copyright © 2007 Eash et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Eash, John
Olsen, Aaron
Breur, Gert
Gerrard, Dave
Hannon, Kevin
FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title_full FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title_fullStr FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title_full_unstemmed FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title_short FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension
title_sort fgfr1 inhibits skeletal muscle atrophy associated with hindlimb suspension
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1853093/
https://www.ncbi.nlm.nih.gov/pubmed/17425786
http://dx.doi.org/10.1186/1471-2474-8-32
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