TGF-β3-ameliorated radiation-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition

Abstract

Objective To detect and analyze the influence of epithelial-mesenchymal transition (EMT) on radiation-induced pulmonary fibrosis and explore whether the anti-fibrosis effect of transforming growth factor-β3 (TGF-β3) is mediated by EMT. Methods C57BL/6 female mice were randomly divided into three groups: control group, irradiation group only (irradiated group), and irradiation and TGF-β3 group (TGF-β3 group). The irradiation group received intraperitoneal injections of 0.5 ml saline, and the TGF-β3 group received intraperitoneal injections of 1 μg/kg human recombinant TGF-β3 every week after single dose of 20 Gy irradiation to their thoraxes. The mice in each group were sacrificed for 1, 3, and 6 months after irradiation. The mouse lung pathological changes were evaluated by hematoxylin-eosin and Masson trichrome. The expression of EMT epithelium-marked protein zonula occludens-1(ZO-1) and interstitial-marked protei N-cadherin were measured by immunohistochemistry. The results were analyzed using Mann-Whitney U test and Fisher's exact probability. Results Alveolar walls thickened, collagen fibers were deposited, and other typical fibrosis changed after irradiation. Unlike those in the irradiation group, pulmonary fibrosis lesions were significantly reduced (Z=-2.562, -2.807, both P<0.05) and collagen deposition was obviously decreased (Z=2.442, 2.529, both P<0.05) in the TGF-β3 group. The expression of ZO-1 was markedly decreased (Z=4.492, 5.831, 6.064, all P<0.05) and the expression of N-cadherin was significantly increased (Z=-3.269, -5.520, -6.063, all P<0.05) in the lung tissues of mice at 1, 3, and 6 months after irradiation. Unlike the irradiation group, the expression of ZO-1 was increased (Z=-2.881, -4.220, -5.695, all P<0.05) and the expression of N-cadherin was decreased (Z=4.546, 3.560, 4.919, all P<0.05) in the TGF-β3 group. The differences were significant. Conclusion TGF-β3 may antagonize radiation-induced pulmonary fibrosis by inhibiting EMT. Key words: Idiopathic pulmonary fibrosis; Radiation injuries, experimental; Transforming growth factor beta 3; Epithelial mesenchymal transition