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.
Bibliographical noteFunding Information:
This study was supported by the Radiation Technology Research and Development Program (NRF-2013M2A2A7042978, 2015M2A2A7A03044831) and by the Nuclear Research and Development Program (NRF-2011-0031695) through the National Research Foundation of Korea, funded by the Ministry of Science, ICT & Future Planning, as well as by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI15C0214).
© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Cell Biology