Targeted expression of IGF-1 transgene to skeletal muscle accelerates muscle and motor neuron regeneration.
Currently, there is no known medical treatment that hastens the repair of damaged nerve and muscle. Using IGF-1 transgenic mice that specifically express human recombinant IGF-1 in skeletal muscle, we test the hypotheses that targeted gene expression of IGF-1 in skeletal muscle enhances motor nerve regeneration after a nerve crush injury. The IGF-1 transgene affects the initiation of the muscle repair process after nerve injury as shown by increased activation of SCA-1positive myogenic stem cells. Increased satellite cell differentiation and proliferation are observed in IGF-1 transgenic mice, shown by increased expression of Cyclin D1, MyoD, and myogenin. Expression of myogenin and nicotinic acetylcholine receptor subunits, initially increased in both wild-type and IGF-1 transgenic mice, are restored to normal levels at a faster rate in IGF-1 transgenic mice, which indicates a rescue of nerve-evoked muscle activity. Expression of the IGF-1 transgene in skeletal muscle results in accelerated recovery of saltatory nerve conduction, increased innervation as detected by neurofilament expression, and faster recovery of muscle mass. These studies demonstrate that local expression of IGF-1 augments the repair of injured nerve and muscle.
Rabinovsky
Eric D
ED
Michael E. Debakey Department of Surgery, Division of Plastic Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. ericr@bcm.tmc.edu
Gelir
Ethem
E
Gelir
Seda
S
Lui
Hui
H
Kattash
Maan
M
DeMayo
Francesco J
FJ
Shenaq
Saleh M
SM
Schwartz
Robert J
RJ
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009046:Motor Neurons / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology*; D009409:Nerve Crush; D009416:Nerve Regeneration; D010525:Peripheral Nerves / Q000502:physiology; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology; D013234:Stem Cells / Q000166:cytology; D019076:Transgenes
D007334:Insulin-Like Growth Factor I