NRF2 deficiency reduces life span of mice administered thoracic irradiation.
NRF2 deficiency reduces life span of mice administered thoracic irradiation.
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DOI：
10.1016/j.freeradbiomed.2011.05.038
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发表时间：
2011-09-15
影响因子：
7.4
通讯作者：
Freeman, Michael L.
中科院分区：
文献类型：
--
作者：
Travis, Elizabeth L.;Rachakonda, Girish;Zhou, Xinhui;Korhonen, Katrina;Sekhar, Konjeti R.;Biswas, Swati;Freeman, Michael L.
关键词：
Subsets of cancer survivors who have been subjected to thoracic irradiation face the prospect of developing pulmonary injury. Radiation-induced pulmonary fibrosis is an insidious injury that presents 6 to 24 months after irradiation and continues to progress over a period of years. TGF-β and reactive oxygen species contribute significantly to the pathogenesis of this injury. The transcription factor NRF2 controls antioxidant gene expression and therefore regulates the cellular oxidant burden. This work demonstrates an additional paradigm for NRF2: suppression of TGF-β-mediated signaling, assessed by measuring expression of a surrogate TGF-β1 target gene (PAI-1) in lung fibroblasts. Thoracic irradiation of Nfe2l2 (−/−) mice resulted in rapid expression of PAI-1 and FSP-1 compare to irradiated wild type mice. Examination of lung tissue 16 weeks after thoracic irradiation of Nfe2l2 (−/−) mice revealed the presence of distended alveoli and decreased numbers of alveoli compared to wild type mice. Suppression of NRF2 expression shortened life span in mice administered 16 Gy to the thorax. Nfe2l2 (+/−) and (−/−) mice exhibited a mean life span of 176 days compared to wild type mice that lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for development of late tissue injury.
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DOI：
10.1164/ajrccm.162.1.9903129
发表时间：
2000-07-01
影响因子：
24.7
作者：
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通讯作者：
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作者：
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影响因子：
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作者：
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