Effects of insulin-like growth factor-1 gene transfer on myosin heavy chains in denervated rat laryngeal muscle.
OBJECTIVE
To determine whether the myotrophic activity of human insulin-like growth factor (hIGF)-1 promotes restoration of normal myosin heavy chain (MHC) composition after nerve injury, MHC composition was analyzed after hIGF-1 gene transfer in denervated rat laryngeal muscle.


METHODS
Animal model to study effects of gene transfer on laryngeal paralysis.


METHODS
In anesthetized rats, the left recurrent and superior laryngeal nerves are cut and suture ligated. A midline thyrotomy is performed, and the thyroarytenoid muscle is injected with a polyvinyl-based formulation containing a muscle specific expression system and hIGF-1 DNA (treatment group) or saline (control group). After 30 days, animals were killed, and the thyroarytenoid muscle was removed and processed for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Densitometric measurements were obtained to determine composition of MHCs.


RESULTS
As previously described, MHC composition in denervated laryngeal muscle was characterized by a decrease in type IIB and IIL and up-regulation of IIA/IIX. Compared with controls, hIGF-1 treated animals demonstrated a significant increase in expression of type IIB and IIL and a significant decrease in expression of type IIA/X.


CONCLUSIONS
These findings suggest that the myotrophic effect of hIGF-1 gene transfer results in normalization of MHC composition in denervated muscle, with suppression of type IIA/X MHC and promotion of type IIL expression.
Flint
Paul W
PW
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, 601 N. Caroline Street, Baltimore, MD 21287, USA. pflint@jhmi.edu
Nakagawa
Hideki
H
Shiotani
Akihiro
A
Coleman
Michael E
ME
O'Malley
Bert W
BW
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D007821:Laryngeal Muscles / Q000294:innervation / Q000378:metabolism*; D009121:Muscle Denervation; D018995:Myosin Heavy Chains / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014826:Vocal Cord Paralysis / Q000628:therapy
D007334:Insulin-Like Growth Factor I; D018995:Myosin Heavy Chains