IGF-1 gene transfer into denervated rat laryngeal muscle

Paul Flint, Akihiro Shiotani, Bert W. O'Malley

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Objectives: To demonstrate gene transfer in rat laryngeal muscle using a reporter gene, β-galactosidase, and a muscle-specific expression system containing the human IGF-1 (hIGF-1) gene sequence and to investigate the myotrophic and neurotrophic effects of hIGF-1 gene transfer in denervated rat laryngeal muscle. Methods: In 8 adult rats, a polyvinyl-based formulation containing β-galactosidase DNA was injected into denervated thyroarytenoid muscle. Twelve animals were similarly administered a polyvinyl-based formulation containing a muscle-specific expression system and hIGF-1 DNA. Twelve animals were injected with isotonic sodium chloride solution, and all animals survived for 1 month. The production of β-galactosidase and hIGF-1 was detected using immunohistochemical techniques. The effects of hIGF-1 on motor endplates and nerve sprouting were assessed using cholinesterase or silver staining and immunostaining for growth-associated protein (GAP-43). Results: β-Galactosidase was detected in 7 of 8 animals by immunostaining, X-gal histochemical staining, or both. In frozen section specimens, hIGE-1 immunoreactivity was positive in 3 of 8 animals. In sequential sections, GAP- 43 was localized to areas of hIGF-1 expression in 2 of the 3 hIGF-1-positive specimens. Increased nerve sprouting and motor endplate contact occurred in 2 of 4 animals treated with hIGF-1. Conclusions: Gene transfer into laryngeal muscle was demonstrated using a polyvinyl-based formulation containing a muscle-specific gene expression system. Preliminary findings indicate a positive effect on motor endplates, nerve sprouting, and the expression of GAP-43 in animals treated with the hIGF-1 vector. This study establishes a foundation for investigating hIGF-1 gene transfer as a novel treatment of laryngeal paralysis. Further studies are necessary to quantify myotrophic and neurotrophic effects and to establish therapeutic benefit.

Original languageEnglish (US)
Pages (from-to)274-279
Number of pages6
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume125
Issue number3
StatePublished - Mar 1999
Externally publishedYes

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Laryngeal Muscles
Insulin-Like Growth Factor I
Galactosidases
Genes
Motor Endplate
Polyvinyls
GAP-43 Protein
Muscles
Vocal Cord Paralysis
Silver Staining
DNA
Cholinesterases
Frozen Sections
Reporter Genes
Sodium Chloride
Staining and Labeling

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

IGF-1 gene transfer into denervated rat laryngeal muscle. / Flint, Paul; Shiotani, Akihiro; O'Malley, Bert W.

In: Archives of Otolaryngology - Head and Neck Surgery, Vol. 125, No. 3, 03.1999, p. 274-279.

Research output: Contribution to journalArticle

Flint, Paul ; Shiotani, Akihiro ; O'Malley, Bert W. / IGF-1 gene transfer into denervated rat laryngeal muscle. In: Archives of Otolaryngology - Head and Neck Surgery. 1999 ; Vol. 125, No. 3. pp. 274-279.
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