Abstract
BackgroundSkeletal 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.MethodsWe examined the effects of ectopic expression of FGFR1 during disuse-mediated skeletal muscle atrophy, utilizing hindlimb suspension and DNA electroporation in mice.ResultsWe 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.ConclusionThese 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.
Highlights
Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age
We found FGFR1 to be expressed in muscle fibers within atrophying muscle, fibers which appeared to be resistant to atrophy
These results confirm previous studies that demonstrate a reduction of protein synthesis that occurs during hind limb suspension [46]. In both weight bearing and suspended gastrocnemius/soleus muscles electroporated with FGFR1, there was an average 16% greater (P < 0.05) tritium incorporated than in contralateral muscles electroporated with control plasmid (Figure 5). These results show that ectopic expression of FGFR1 stimulates protein synthesis in skeletal muscle fibers in vivo
Summary
Skeletal muscle atrophy can occur under many different conditions, including prolonged disuse or immobilization, cachexia, cushingoid conditions, secondary to surgery, or with advanced age. Additional changes noted in atrophied skeletal muscle are a decrease in overall nucleic acid quantities, as well as a loss of myonuclei [4]. These physical characteristics are accompanied by decreased muscle strength [5], and increased propensity to muscle fatigue [6]. Several strategies have been used in an attempt to attenuate or reverse muscle atrophy associated with disuse. The success of these attempts appears to depend on the action of growth factors used, the delivery system employed, and the model of atrophy studied. In certain clinical situations such as bed-ridden or casted patients, exercise is not an option when attempting to attenuate muscle atrophy
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