Histopathologic amelioration of fibroproliferative change in rat irradiated lung using soluble transforming growth factor-beta (TGF-β) receptor mediated by adenoviral vector

To investigate whether an adenoviral-mediated soluble transforming growth factor-beta (TGF-β) type II receptor could ameliorate fibroproliferative change in rat irradiated lung. We used an adenoviral vector expressing a soluble TGF-β receptor (AdTβ-ExR), which adsorbs TGF-β and inhibits the function of the wild-type receptor as a dominant-negative mutant. Rats were i.v. injected with either 0.5 mL of AdTβ-ExR (1.0 × 10 9 plaque-forming units/mL) or AdLacZ (1.0 × 10 9 plaque-forming units/mL), a control adenovirus expressing bacterial β-galactosidase, or saline, then 3 days later they received 4-MV X-ray irradiation of 30 Gy in a single fraction to the right lung. Eight weeks after irradiation, the rats were killed, and their right lungs were examined histopathologically. The respiratory rates of all rats were observed with a charge-coupled device video system before the rats were irradiated and killed. A significant increase in breathing rates was observed in the saline- or AdLacZ-infected rats. The respiratory rate of the AdTβ-ExR–treated rats was significantly lower than that in the saline- or AdLacZ-infected rats. Fibroproliferative change in the irradiated lung was markedly reduced in the AdTβ-ExR–treated rats in comparison with the saline- or AdLacZ-infected rats. With respect to active TGF-β1 expression, myofibroblast proliferation, and macrophage/monocyte infiltration, the findings were identical to those for fibroproliferative change. Our results indicate that TGF-β plays a critical role in radiation-induced fibroproliferation of the lung and suggest that the adenoviral-mediated soluble TGF-β receptor may have potential for use in the amelioration of this intractable pulmonary damage.