title: Effects of NOX1 on fibroblastic changes of endothelial cells in radiation‑induced pulmonary fibrosis.
abstract: Lung fibrosis is a major complication in radiation‑induced lung damage following thoracic radiotherapy, while the underlying mechanism has remained to be elucidated. The present study performed immunofluorescence and immunoblot assays on irradiated human pulmonary artery endothelial cells (HPAECs) with or without pre‑treatment with VAS2870, a novel NADPH oxidase (NOX) inhibitor, or small hairpin (sh)RNA against NOX1, ‑2 or ‑4. VAS2870 reduced the cellular reactive oxygen species content induced by 5 Gy radiation in HPAECs and inhibited phenotypic changes in fibrotic cells, including increased alpha smooth muscle actin and vimentin, and decreased CD31 and vascular endothelial cadherin expression. These fibrotic changes were significantly inhibited by treatment with NOX1 shRNA, but not by NOX2 or NOX4 shRNA. Next, the role of NOX1 in pulmonary fibrosis development was assessed in the lung tissues of C57BL/6J mice following thoracic irradiation using trichrome staining. Administration of an NOX1‑specific inhibitor suppressed radiation‑induced collagen deposition and fibroblastic changes in the endothelial cells (ECs) of these mice. The results suggested that radiation‑induced pulmonary fibrosis may be efficiently reduced by specific inhibition of NOX1, an effect mediated by reduction of fibrotic changes of ECs.
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Seo-Hyun
authors.initials: SH
authors.lastname: Choi
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Miseon
authors.initials: M
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Hae-June
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Eun-Ho
authors.initials: EH
authors.lastname: Kim
authors.affiliation: Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Yoon-Jin
authors.initials: YJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D002460:Cell Line; D042783:Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000201:enzymology* / Q000473:pathology; D011832:Radiation Injuries / Q000201:enzymology* / Q000473:pathology; D014230:Triazoles / Q000494:pharmacology
chemical_list: C511179:3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo(4,5-d)pyrimidine; D001583:Benzoxazoles; D014230:Triazoles; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C000614711:NOX1 protein, mouse