FGFR1 inhibits skeletal muscle atrophy associated with hindlimb suspension

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BMC Musculoskelet Disord. 2007 Apr 10;8:32.

FGFR1 inhibits skeletal muscle atrophy associated with hindlimb

suspension.

Eash J, Olsen A, Breur G, Gerrard D, Hannon K.

Department of Basic Medical Sciences, Purdue University, West

Lafayette, Indiana 47907, USA.

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.