PURPOSE: To investigate whether an adenoviral-mediated soluble transforming growth factor-beta (TGF-beta) type II receptor could ameliorate fibroproliferative change in rat irradiated lung. METHODS AND MATERIALS: We used an adenoviral vector expressing a soluble TGF-beta receptor (AdT beta-ExR), which adsorbs TGF-beta 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 AdT beta-ExR (1.0 x 10(9) plaque-forming units/mL) or AdLacZ (1.0 x 10(9) plaque-forming units/mL), a control adenovirus expressing bacterial beta-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. RESULTS: A significant increase in breathing rates was observed in the saline- or AdLacZ-infected rats. The respiratory rate of the AdT beta-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 AdT beta-ExR-treated rats in comparison with the saline- or AdLacZ-infected rats. With respect to active TGF-beta 1 expression, myofibroblast proliferation, and macrophage/monocyte infiltration, the findings were identical to those for fibroproliferative change. CONCLUSIONS: Our results indicate that TGF-beta plays a critical role in radiation-induced fibroproliferation of the lung and suggest that the adenoviral-mediated soluble TGF-beta receptor may have potential for use in the amelioration of this intractable pulmonary damage.
PURPOSE: To investigate whether an adenoviral-mediated soluble transforming growth factor-beta (TGF-beta) type II receptor could ameliorate fibroproliferative change in rat irradiated lung. METHODS AND MATERIALS: We used an adenoviral vector expressing a soluble TGF-beta receptor (AdT beta-ExR), which adsorbs TGF-beta 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 AdT beta-ExR (1.0 x 10(9) plaque-forming units/mL) or AdLacZ (1.0 x 10(9) plaque-forming units/mL), a control adenovirus expressing bacterial beta-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. RESULTS: A significant increase in breathing rates was observed in the saline- or AdLacZ-infected rats. The respiratory rate of the AdT beta-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 AdT beta-ExR-treated rats in comparison with the saline- or AdLacZ-infected rats. With respect to active TGF-beta 1 expression, myofibroblast proliferation, and macrophage/monocyte infiltration, the findings were identical to those for fibroproliferative change. CONCLUSIONS: Our results indicate that TGF-beta plays a critical role in radiation-induced fibroproliferation of the lung and suggest that the adenoviral-mediated soluble TGF-beta receptor may have potential for use in the amelioration of this intractable pulmonary damage.
Authors: Elizabeth L Travis; Girish Rachakonda; Xinhui Zhou; Katrina Korhonen; Konjeti R Sekhar; Swati Biswas; Michael L Freeman Journal: Free Radic Biol Med Date: 2011-06-12 Impact factor: 7.376
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Authors: Michael J Gough; Marka R Crittenden; MaryClare Sarff; Puiyi Pang; Steven K Seung; John T Vetto; Hong-Ming Hu; William L Redmond; John Holland; Andrew D Weinberg Journal: J Immunother Date: 2010-10 Impact factor: 4.456
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Authors: Feng-Ming Spring Kong; Lujun Zhao; Luhua Wang; Yuhchyau Chen; Jie Hu; Xiaolong Fu; Chunxue Bai; Li Wang; Theodore S Lawrence; Mitchell S Anscher; Adam Dicker; Paul Okunieff Journal: Transl Lung Cancer Res Date: 2017-12