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Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis

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 airwa...

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Autores principales: Mizokami, Daisuke, Araki, Koji, Tanaka, Nobuaki, Suzuki, Hiroshi, Tomifuji, Masayuki, Yamashita, Taku, Ueda, Yasuji, Shimada, Hideaki, Matsushita, Kazuyuki, Shiotani, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287628/
https://www.ncbi.nlm.nih.gov/pubmed/25569246
http://dx.doi.org/10.1371/journal.pone.0116279
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author Mizokami, Daisuke
Araki, Koji
Tanaka, Nobuaki
Suzuki, Hiroshi
Tomifuji, Masayuki
Yamashita, Taku
Ueda, Yasuji
Shimada, Hideaki
Matsushita, Kazuyuki
Shiotani, Akihiro
author_facet Mizokami, Daisuke
Araki, Koji
Tanaka, Nobuaki
Suzuki, Hiroshi
Tomifuji, Masayuki
Yamashita, Taku
Ueda, Yasuji
Shimada, Hideaki
Matsushita, Kazuyuki
Shiotani, Akihiro
author_sort Mizokami, Daisuke
collection PubMed
description 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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spelling pubmed-42876282015-01-12 Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis Mizokami, Daisuke Araki, Koji Tanaka, Nobuaki Suzuki, Hiroshi Tomifuji, Masayuki Yamashita, Taku Ueda, Yasuji Shimada, Hideaki Matsushita, Kazuyuki Shiotani, Akihiro PLoS One Research Article 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. Public Library of Science 2015-01-08 /pmc/articles/PMC4287628/ /pubmed/25569246 http://dx.doi.org/10.1371/journal.pone.0116279 Text en © 2015 Mizokami et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Mizokami, Daisuke
Araki, Koji
Tanaka, Nobuaki
Suzuki, Hiroshi
Tomifuji, Masayuki
Yamashita, Taku
Ueda, Yasuji
Shimada, Hideaki
Matsushita, Kazuyuki
Shiotani, Akihiro
Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title_full Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title_fullStr Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title_full_unstemmed Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title_short Gene Therapy of c-myc Suppressor FUSE-Binding Protein-Interacting Repressor by Sendai Virus Delivery Prevents Tracheal Stenosis
title_sort gene therapy of c-myc suppressor fuse-binding protein-interacting repressor by sendai virus delivery prevents tracheal stenosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287628/
https://www.ncbi.nlm.nih.gov/pubmed/25569246
http://dx.doi.org/10.1371/journal.pone.0116279
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