Abstract
Radiation-induced skin injury (RISI) commonly occur in cancer patients who received radiotherapy and is one of the first clinical symptoms after suffering from nuclear exposure. Oxidative damage is the major causes of RISI. Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a key mediator of the cellular antioxidant response. However, whether Nrf2 can alleviate RISI after high-dose irradiation remains unknown. In this study, we demonstrated that Nrf2-deficient (Nrf2 -/-) mice were susceptible to high-dose irradiation and adenovirus-mediated overexpression of Nrf2 (ad-Nrf2) protected against radiation in skin cells. Overexpression of Nrf2 attenuated the severity of skin injury after high-dose electron beam irradiation. To uncover the mechanisms of Nrf2 involved in RISI, mRNA sequencing technology was performed to analyze the mRNA expression profiles of Ad-Nrf2 skin cells following radiation. The results revealed that a total of 127 genes were significantly changed, 55 genes were upregulated, and 72 genes were downregulated after Nrf2 overexpression. GSEA showed that Nrf2 was associated with positive regulation of genes involved in the reactive oxygen species pathway after radiation. Taken together, this study illustrated the role of Nrf2 in RISI and provided potentially strategies for ameliorating RISI.
Highlights
Radiation is widely used in industry, medicine and science and may significantly increase uncontrolled exposure to radiation [1, 2]
We found that skin tissues and primary skin cells from Nuclear factor erythroid 2-related factor 2 (Nrf2)-deficient (Nrf2-/-) mice were more susceptible to 20 Gy irradiation than those from WT (Nrf2+/+) mice
Skin effects can be divided into acute reactions, which occur within days of initiating exposure, and late effects, which often become apparent months to years after irradiation [23, 24]
Summary
Radiation is widely used in industry, medicine and science and may significantly increase uncontrolled exposure to radiation [1, 2]. Since the skin is the first tissue through which external radiation particles enter the human body, it is vulnerable to radiation-induced injury. Radiation-induced dermatitis remains a serious concern that may limit the duration and dose of radiotherapy [3, 5]. Radiation can both directly induce DNA double strand breaks (DSBs) and indirectly produce reactive oxygen species (ROS) and reactive nitrogen species (RNS), including hydroxyl radicals, superoxide anions, hydrogen peroxide and nitrogen dioxide. Nrf Ameliorates Radiation-Induced Skin Injury [6, 7].
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