Abstract |
Acquired tracheal stenosis remains a challenging problem for otolaryngologists. The objective of this study was to determine whether the Sendai virus (SeV)-mediated c-myc suppressor, a far upstream element (FUSE)- binding protein ( FBP)-interacting repressor (FIR), modulates wound healing of the airway mucosa, and whether it prevents tracheal stenosis in an animal model of induced mucosal injury. A fusion gene-deleted, non-transmissible SeV vector encoding FIR (FIR-SeV/ΔF) was prepared. Rats with scraped airway mucosae were administered FIR-SeV/ΔF through the tracheostoma. The pathological changes in the airway mucosa and in the tracheal lumen were assessed five days after scraping. Untreated animals showed hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition causing lumen stenosis. By contrast, the administration of FIR-SeV/ΔF decreased the degree of tracheal stenosis (P < 0.05) and improved the survival rate (P < 0.05). Immunohistochemical staining showed that c-Myc expression was downregulated in the tracheal basal cells of the FIR-SeV/ΔF-treated animals, suggesting that c-myc was suppressed by FIR-SeV/ΔF in the regenerating airway epithelium of the injured tracheal mucosa. The airway-targeted gene therapy of the c-myc suppressor FIR, using a recombinant SeV vector, prevented tracheal stenosis in a rat model of airway mucosal injury.
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Authors | Daisuke Mizokami, Koji Araki, Nobuaki Tanaka, Hiroshi Suzuki, Masayuki Tomifuji, Taku Yamashita, Yasuji Ueda, Hideaki Shimada, Kazuyuki Matsushita, Akihiro Shiotani |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 1
Pg. e0116279
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 25569246
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Proto-Oncogene Proteins c-myc
- RNA Splicing Factors
- RNA-Binding Proteins
- Repressor Proteins
- poly-U binding splicing factor 60KDa
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Topics |
- Animals
- Disease Models, Animal
- Female
- Genetic Therapy
- Genetic Vectors
(genetics, metabolism)
- Immunohistochemistry
- Kaplan-Meier Estimate
- Proto-Oncogene Proteins c-myc
(genetics)
- RNA Splicing Factors
- RNA-Binding Proteins
(genetics)
- Rats
- Rats, Sprague-Dawley
- Repressor Proteins
(genetics)
- Sendai virus
(genetics)
- Trachea
(metabolism)
- Tracheal Stenosis
(mortality, pathology, therapy)
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