Insulin-like growth factor-I gene transfer by electroporation prevents skeletal muscle atrophy in glucocorticoid-treated rats

Abstract

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. Bexamethasone 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 μm2, 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 μm2, P < 0.05) were increased in the TA muscle electroporated with IGF-IDNA, 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. Copyright © 2005 by The Endocrine Society.