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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)711-719
Number of pages9
JournalJournal of Cellular and Molecular Medicine
Volume21
Issue number4
DOIs
Publication statusPublished - 2017 Apr 1

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Noxae
Lung Injury
Lung
Radiation
Apoptosis Regulatory Proteins
Fibrosis
Apoptosis
Cell Death
X-Rays
Alveolar Epithelial Cells
Pulmonary Fibrosis
Inbred C57BL Mouse
Small Interfering RNA
Reactive Oxygen Species
Theoretical Models
Collagen
Fibroblasts
Pathology

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

Cite this

Kim, Jee Youn ; An, Yong Min ; Choi, Won Hoon ; Kim, Jin Mo ; Cho, Samju ; Yoo, Byung Rok ; Kang, Jeong Wook ; Lee, Yun Sil ; Lee, Yoon Jin ; Cho, Jaeho. / Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury. In: Journal of Cellular and Molecular Medicine. 2017 ; Vol. 21, No. 4. pp. 711-719.
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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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Kim, JY, An, YM, Choi, WH, Kim, JM, Cho, S, Yoo, BR, Kang, JW, Lee, YS, Lee, YJ & Cho, J 2017, 'Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury', Journal of Cellular and Molecular Medicine, vol. 21, no. 4, pp. 711-719. https://doi.org/10.1111/jcmm.13014

Pro-apoptotic Noxa is involved in ablative focal irradiation-induced lung injury. / Kim, Jee Youn; An, Yong Min; Choi, Won Hoon; Kim, Jin Mo; Cho, Samju; Yoo, Byung Rok; Kang, Jeong Wook; Lee, Yun Sil; Lee, Yoon Jin; Cho, Jaeho.

In: Journal of Cellular and Molecular Medicine, Vol. 21, No. 4, 01.04.2017, p. 711-719.

Research output: Contribution to journalArticle

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AU - An, Yong Min

AU - Choi, Won Hoon

AU - Kim, Jin Mo

AU - Cho, Samju

AU - Yoo, Byung Rok

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AU - Lee, Yun Sil

AU - Lee, Yoon Jin

AU - Cho, Jaeho

PY - 2017/4/1

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N2 - 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.

AB - 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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