کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909146 1046709 2011 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
NRF2 deficiency reduces life span of mice administered thoracic irradiation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
NRF2 deficiency reduces life span of mice administered thoracic irradiation
چکیده انگلیسی

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 compared 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 Nfe2l2−/− mice exhibited a mean life span of 176 days compared to wild-type mice, which lived an average of 212 days. These novel results identify NRF2 as a susceptibility factor for the development of late tissue injury.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 51, Issue 6, 15 September 2011, Pages 1175–1183
نویسندگان
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