title: Reduction of fibroproliferative changes in irradiated rat lung with soluble transforming growth factor-β receptor.
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.
authors.affiliation: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Nishioka
authors.affiliation: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kariya
authors.affiliation: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Hamada
authors.affiliation: Department of Diagnostic Radiology and Radiation Oncology, Kochi University, School of Medicine, Nankoku, Kochi 783‑8505, Japan.
authors.forename: Munenobu
authors.initials: M
authors.lastname: Nogami
authors.affiliation: Department of Radiation Oncology, Shimane University, Izumo, Shimane 693-8501, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Inomata
authors.affiliation: Department of Biochemistry and Molecular Pathophysiology, University of Occupational and Environmental Health, School of Medicine, Kitakyusyu, Fukuoka 807-8556, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Ueno
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005355:Fibrosis; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology* / Q000528:radiation effects; D008264:Macrophages / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011833:Radiation Injuries, Experimental; D051381:Rats; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II