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

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)- type II receptor. Replication-defective adenoviral vectors expressing a type II human TGF- receptor (AdT-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 AdT-ExR, respectively. To analyze the TGF- 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- 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- 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- receptor may be effective in reducing the established pulmonary fibrosis caused by radiation.