title: FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA. john.eash@novartis.com <john.eash@novartis.com>
authors.forename: John
authors.initials: J
authors.lastname: Eash
authors.forename: Aaron
authors.initials: A
authors.lastname: Olsen
authors.forename: Gert
authors.initials: G
authors.lastname: Breur
authors.forename: Dave
authors.initials: D
authors.lastname: Gerrard
authors.forename: Kevin
authors.initials: K
authors.lastname: Hannon
mesh_terms: D000818:Animals; D004247:DNA / Q000493:pharmacokinetics; D018274:Electroporation; D051519:Fibroblast Growth Factor 4 / Q000235:genetics / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018014:Gene Transfer Techniques; D019417:Hindlimb Suspension; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution
chemical_list: D051519:Fibroblast Growth Factor 4; D009124:Muscle Proteins; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D004247:DNA; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1