title: The role of alveolar epithelium in radiation-induced lung injury.
abstract: Pneumonitis and fibrosis are major lung complications of irradiating thoracic malignancies. In the current study, we determined the effect of thoracic irradiation on the lungs of FVB/N mice. Survival data showed a dose-dependent increase in morbidity following thoracic irradiation with single (11-13 Gy) and fractionated doses (24-36 Gy) of (137)Cs γ-rays. Histological examination showed a thickening of vessel walls, accumulation of inflammatory cells, collagen deposition, and regional fibrosis in the lungs 14 weeks after a single 12 Gy dose and a fractionated 30 Gy dose; this damage was also seen 5 months after a fractionated 24 Gy dose. After both single and fractionated doses, i] aquaporin-5 was markedly decreased, ii] E-cadherin was reduced and iii] prosurfactant Protein C (pro-SP-c), the number of pro-SP-c(+) cells and vimentin expression were increased in the lungs. Immunofluorescence analysis revealed co-localization of pro-SP-c and α-smooth muscle actin in the alveoli after a single dose of 12 Gy. These data suggest that, i] the FVB/N mouse strain is sensitive to thoracic radiation ii] aquaporin-5, E-cadherin, and pro-SP-c may serve as sensitive indicators of radiation-induced lung injury; and iii] the epithelial-to-mesenchymal transition may play an important role in the development of radiation-induced lung fibrosis.
authors: Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
authors: Celine
authors: C
authors: Almeida
authors: Devipriya
authors: D
authors: Nagarajan
authors: Jian
authors: J
authors: Tian
authors: Sofia Walder
authors: SW
authors: Leal
authors: Kenneth
authors: K
authors: Wheeler
authors: Michael
authors: M
authors: Munley
authors: William
authors: W
authors: Blackstock
authors: Weiling
authors: W
authors: Zhao
mesh_terms: D000818:Animals; D051402:Aquaporin 5 / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D004848:Epithelium / Q000473:pathology* / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D055370:Lung Injury / Q000150:complications* / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D021381:Protein Transport / Q000528:radiation effects; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D037721:Pulmonary Surfactant-Associated Protein C / Q000378:metabolism; D011832:Radiation Injuries / Q000150:complications* / Q000473:pathology*; D016019:Survival Analysis; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D051402:Aquaporin 5; D015820:Cadherins; D037721:Pulmonary Surfactant-Associated Protein C; D053773:Transforming Growth Factor beta1; D019010:Vascular Cell Adhesion Molecule-1; D014746:Vimentin