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Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury

Authors
 Jee‐Youn Kim  ;  Yong‐Min An  ;  Won Hoon Choi  ;  Jin‐Mo Kim  ;  Samju Cho  ;  Byung Rok Yoo  ;  Jeong Wook Kang  ;  Yun‐Sil Lee  ;  Yoon‐Jin Lee  ;  Jaeho Cho 
Citation
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol.21(4) : 711-719, 2017 
Journal Title
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 
ISSN
 1582-1838 
Issue Date
2017
MeSH
Animals ; Apoptosis*/radiation effects ; Biomarkers/metabolism ; Cell Line ; Dose-Response Relationship, Radiation ; Gene Knockdown Techniques ; Humans ; Immunohistochemistry ; Lung/pathology ; Lung/radiation effects ; Lung Injury/etiology* ; Lung Injury/metabolism* ; Lung Injury/pathology ; Mice ; Promoter Regions, Genetic/genetics ; Proto-Oncogene Proteins c-bcl-2/genetics ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Pulmonary Fibrosis/etiology ; Pulmonary Fibrosis/pathology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Radiation Injuries/complications* ; Radiation Injuries/metabolism* ; Radiation Injuries/pathology ; Reactive Oxygen Species/metabolism ; X-Rays
Keywords
Noxa ; apoptosis ; lung injury ; radiation
Abstract
Although lung injury including fibrosis is a well-documented side effect of lung irradiation, the mechanisms underlying its pathology are poorly understood. X-rays are known to cause apoptosis in the alveolar epithelial cells of irradiated lungs, which results in fibrosis due to the proliferation and differentiation of fibroblasts and the deposition of collagen. Apoptosis and BH3-only pro-apoptotic proteins have been implicated in the pathogenesis of pulmonary fibrosis. Recently, we have established a clinically analogous experimental model that reflects focal high-dose irradiation of the ipsilateral lung. The goal of this study was to elucidate the mechanism underlying radiation-induced lung injury based on this model. A radiation dose of 90 Gy was focally delivered to the left lung of C57BL/6 mice for 14 days. About 9 days after irradiation, the mice began to show increased levels of the pro-apoptotic protein Noxa in the irradiated lung alongside increased apoptosis and fibrosis. Suppression of Noxa expression by small interfering RNA protected cells from radiation-induced cell death and decreased expression of fibrogenic markers. Furthermore, we showed that reactive oxygen species participate in Noxa-mediated, radiation-induced cell death. Taken together, our results show that Noxa is involved in X-ray-induced lung injury.
Files in This Item:
T201700672.pdf Download
DOI
10.1111/jcmm.13014.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Cho, Sam Ju(조삼주)
Cho, Jae Ho(조재호) ORCID logo https://orcid.org/0000-0001-9966-5157
Choi, Won Hoon(최원훈)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154496
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