Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats.
Catabolic states caused by injury are characterized by a loss of skeletal muscle. The anabolic action of IGF-I on muscle and the reduction of its muscle content in response to injury suggest that restoration of muscle IGF-I content might prevent skeletal muscle loss caused by injury. We investigated whether local overexpression of IGF-I protein by gene transfer could prevent skeletal muscle atrophy induced by glucocorticoids, a crucial mediator of muscle atrophy in catabolic states. Localized overexpression of IGF-I in tibialis anterior (TA) muscle was performed by injection of IGF-I cDNA followed by electroporation 3 d before starting dexamethasone injections (0.1 mg/kg.d sc). A control plasmid was electroporated in the contralateral TA muscle. Dexamethasone induced atrophy of the TA muscle as illustrated by reduction in muscle mass (403 +/- 11 vs. 461 +/- 19 mg, P < 0.05) and fiber cross-sectional area (1759 +/- 131 vs. 2517 +/- 93 mum(2), P < 0.05). This muscle atrophy was paralleled by a decrease in the IGF-I muscle content (7.2 +/- 0.9 vs. 15.7 +/- 1.4 ng/g of muscle, P < 0.001). As the result of IGF-I gene transfer, the IGF-I muscle content increased 2-fold (15.8 +/- 1.2 vs. 7.2 +/- 0.9 ng/g of muscle, P < 0.001). In addition, the muscle mass (437 +/- 8 vs. 403 +/- 11 mg, P < 0.01) and the fiber cross-sectional area (2269 +/- 129 vs. 1759 +/- 131 mum(2), P < 0.05) were increased in the TA muscle electroporated with IGF-I DNA, compared with the contralateral muscle electroporated with a control plasmid. Our results show therefore that IGF-I gene transfer by electroporation prevents muscle atrophy in glucocorticoid-treated rats. Our observation supports the important role of decreased muscle IGF-I in the muscle atrophy caused by glucocorticoids.
Schakman
O
O
Unité de Diabétologie et Nutrition, Université Catholique de Louvain, 54 avenue Hippocrate, B-1200 Brussels, Belgium.
Gilson
H
H
de Coninck
V
V
Lause
P
P
Verniers
J
J
Havaux
X
X
Ketelslegers
J M
JM
Thissen
J P
JP
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D018274:Electroporation; D015316:Genetic Therapy; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D008297:Male; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000473:pathology*; D009133:Muscular Atrophy / Q000628:therapy*; D009210:Myofibrils / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection
D009124:Muscle Proteins; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone