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

Title
Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury
Authors
Kim, Jee-YounAn, Yong-MinChoi, Won HoonKim, Jin-MoCho, SamjuYoo, Byung RokKang, Jeong WookLee, Yun-SilLee, Yoon-JinCho, Jaeho
Ewha Authors
이윤실
SCOPUS Author ID
이윤실scopus
Issue Date
2017
Journal Title
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
ISSN
1582-4934JCR Link
Citation
vol. 21, no. 4, pp. 711 - 719
Keywords
Noxaradiationlung injuryapoptosis
Publisher
WILEY
Indexed
SCIE; SCOPUS WOS scopus
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.
DOI
10.1111/jcmm.13014
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약학대학 > 약학과 > Journal papers
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