Pro‐apoptotic Noxa is involved in ablative focal irradiation‐induced lung injury |
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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 |
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Affiliation: | 1. Department of Radiation Oncology, Yonsei University College of Medicine, Seoul, South Korea;2. College of Pharmacy and Division of Life and Pharmaceutical Science, Ewha Womans University, Seoul, South Korea;3. Division of Radiation Effects, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea |
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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. |
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Keywords: | Noxa radiation lung injury apoptosis |
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