Reduction of fibroproliferative changes in irradiated rat lung with soluble transforming growth factor-β receptor

Nishioka,Akihito; Ogawa,Yasuhiro; Kariya,Shinji; Hamada,Norihiko; Nogami,Munenobu; Inomata,Taisuke; Ueno,Hikaru

doi:10.3892/mmr.2014.3064

Reduction of fibroproliferative changes in irradiated rat lung with soluble transforming growth factor-β receptor

Authors:
- Akihito Nishioka
- Yasuhiro Ogawa
- Shinji Kariya
- Norihiko Hamada
- Munenobu Nogami
- Taisuke Inomata
- Hikaru Ueno
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Affiliations: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan, Department of Radiation Oncology, Shimane University, Izumo, Shimane 693-8501, Japan, Department of Biochemistry and Molecular Pathophysiology, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu, Fukuoka 807-8556, Japan
Published online on: December 9, 2014 https://doi.org/10.3892/mmr.2014.3064
Pages: 2659-2663

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Abstract

The present study investigated whether established fibroproliferative changes in the irradiated rat lung are histopathologically reduced by an adenovirus‑mediated soluble transforming growth factor (TGF)‑β type II receptor. Replication‑defective adenoviral vectors expressing a type II human TGF‑β receptor (AdTβ‑ExR) were prepared. Male Fisher‑344 rats were divided into the C, R and R + T groups. The rats in the C group did not receive irradiation or treatment. The rats in the R and R + T group each received 30 Gy irradiation to the right lung. Eight weeks following irradiation, the rats in the R and R + T group were treated with saline or AdTβ‑ExR, respectively. To analyze the TGF‑β expression, myofibroblast proliferation and macrophage/monocyte infiltration, sections of the lung were immunohistochemically stained at 16 weeks following irradiation. Silver staining was performed for semi‑quantitative evaluation of the fibroproliferative changes. Definitive TGF‑β expression, myofibroblast proliferation and macrophage/monocyte infiltration were observed in the lungs of the R group, but were significantly lower in the lungs of the R + T group. With respect to the fibroproliferative changes, the proportion of red‑stained areas in the R + T group was markedly lower than that in the R group. These data indicate that fibroproliferative changes induced by radiation are reversible and that TGF‑β has a critical role in fibroproliferative changes in the irradiated lung. The present results suggest that gene therapy with an adenoviral vector expressing a soluble TGF‑β receptor may be effective in reducing the established pulmonary fibrosis caused by radiation.

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