Effects of Insulin-Like Growth Factor-1 Gene Transfer on Myosin Heavy Chains in Denervated Rat Laryngeal Muscle

Paul W. Flint, Hideki Nakagawa, Akihiro Shiotani, Michael E. Coleman, Bert W. O'Malley

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Objectives/Hypothesis: 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. Study Design: 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.

Original languageEnglish (US)
Pages (from-to)368-371
Number of pages4
JournalLaryngoscope
Volume114
Issue number2
DOIs
StatePublished - Feb 1 2004

Keywords

  • Gene therapy
  • IGF-1
  • Laryngeal paralysis
  • Muscle
  • Myosin heavy chain

ASJC Scopus subject areas

  • Otorhinolaryngology

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