alexa Adenovirus-Mediated Bcl-Xl Gene Therapy Combined with P
ISSN: 2157-7412

Journal of Genetic Syndromes & Gene Therapy
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Research Article

Adenovirus-Mediated Bcl-Xl Gene Therapy Combined with Pronase Treatment Protects the Small Intestine from Radiation-Induced Enteritis in Mouse Model

Fumikazu Koyama1,2*, Kazuaki Uchimoto1, Hisao Fujii2, Hirofumi Hamada3, Kazuo Ohashi4, Takeo Nomi1, Tadashi Nakagawa1, Shinji Nakamura1, Takeshi Ueda1 and Yoshiyuki Nakajima1

1Department of Surgery, Nara Medical University, 840 Shijo-cho Kashihara City, Nara 634-8522, Japan

2Department of Endoscopy and Ultrasound, Nara Medical University Hospital, 840 Shijo-cho Kashihara City, Nara 634-8522, Japan

3Laboratory of Oncology, Department of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji-city, Tokyo 192-0392, Japan

4National Institute of Biomedical Innovation, 7-6-8 Asagi Saito, Ibaraki-city, Osaka 567-0085, Japan

*Corresponding Author:
Fumikazu Koyama
Department of Surgery
Nara Medical University
840 Shijo-cho Kashihara City
Nara 634-8522, Japan
Tel: +81-744-22-3051
Fax: +81-744-24-6866
E-mail: [email protected]

Received date: March 27, 2014; Accepted date:September 03, 2014; Published date: September 09, 2014

Citation: Fumikazu Koyama, Kazuaki Uchimoto, Hisao Fujii, Hirofumi Hamada, Kazuo Ohashi, et al. (2014) Adenovirus-Mediated Bcl-Xl Gene Therapy Combined with Pronase Treatment Protects the Small Intestine from Radiation-Induced Enteritis in Mouse Model. J Genet Syndr Gene Ther 5:239. doi: 10.4172/2157-7412.1000239

Copyright: © 2014 Koyama F, et al. 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 credited.

 

Abstract

Intestinal injury is a major side effect of radiation treatment for many malignancies. The present study investigated whether transducing Bcl-xL, a potent anti-apoptotic gene, into intestinal epithelial cells would exert protective effects against radiation-induced acute injuries. Methods: Adenoviral vectors containing the human Bcl-xL gene (AxCABclxL) or β-galactosidase gene (AxCAlacZ) driven by the CAG promoter were generated. To increase transduction efficiency into the mucosal epithelium, the intraluminal space of the small intestine of mice was washed with buffered-saline and mucus components were digested with Pronase MS®. Gene transduction was performed by injecting 2×108 pfu adenoviral vector into the pre-treated small intestine. Transduction efficiency was examined by X-gal staining 24 hours after AxCAlacZ infection. Radiation-induced acute injury of the small intestine was induced by whole body irradiation (15 Gy) performed 24 hours after adenoviral vector infection. Apoptotic epithelial cells were visualized by TUNEL assay. Morphological analysis was assessed by histological examination. Results: Successful transduction after Pronase MS® treatment was achieved in the basal crypt epithelial cells in the ileum, thought to be the location of stem cells, as determined by X-gal staining. The AxCABclxL group demonstrated significantly fewer radiation-induced apoptotic mucosal epithelial cells when compared with the other two groups at 6 hours after irradiation (p<0.05). At 72 hours after irradiation, the morphological appearance of the small intestine in the AxCABclxL group showed significantly less radiation damage in terms of mucosal thickness (p<0.001). Conclusions: The present study indicates that Bcl-xL gene expression using adenoviral vector-mediated transduction is a valuable approach to prevent intestinal injury caused by radiation exposure.

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