Ionizing radiation induces cutaneous lipid remolding and skin adipocytes confer protection against radiation-induced skin injury

Xiao, Yuji; Mo, Wei; Jia, Haiying; Yu, Daojiang; Qiu, Yuyou; Jiao, Yang; Zhu, Wei; Koide, Hiroshi; Cao, Jianping; Zhang, Shuyu

doi:10.1016/j.jdermsci.2020.01.009

Cited by 25 publications

(21 citation statements)

References 36 publications

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“…A 3-cmthick piece of lead was used to shield the rats and localize the radiation field (3 cm × 4 cm). A single dose of 45 Gy irradiation [23][24][25] was administered to the hindlimb region of the SD rats at a dose rate of 750 cGy/min using a 6-MeV electron beam accelerator (Clinac 2100EX, Varian Medical Systems, Inc., CA, USA). This dose was selected because it can significantly induce skin injury [23][24][25][26].…”

Section: Animal Studiesmentioning

confidence: 99%

Fenofibrate Attenuates Radiation-Induced Oxidative Damage to the Skin through Fatty Acid Binding Protein 4 (FABP4)

Sun¹,

Song²,

Sheng³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Radiation facilities and radioactive materials have been widely used in military, industry, medicine, science and nuclear facilities, which has significantly increased the potential of large-scale, uncontrolled exposure to radiation. The skin is one of the radiosensitive organ systems and radiation-induced skin injury remains a serious concern after ionizing radiation exposure. Our previous report indicates the involvement of the peroxisome proliferator-activated receptor pathway in the response of skin tissues to ionizing radiation. PPARα is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. However, the protection of fenofibrate against ionizing radiation in skin keratinocytes and fibroblasts has not been described. Methods: The PPARα mRNA levels in irradiated and nonirradiated skin tissues of rats were determined by real-time assay. The expression of PPARα, and FABP4 were evaluated by western blot and IHC assay. The cell proliferation was detected by colony formation. The γH2AX foci and ROS levels in irradiated WS1 cells with FABP4 overexpression than in control cells were performed by Immunofluorescence assay. Results: We found that PPARα expression was lower in the irradiated skin tissues of mouse, rat, monkey, and human patients than in their nonirradiated counterparts. PPARα fenofibrate significantly decreased radiation-induced ROS and apoptosis in a dose-dependent manner in human keratinocyte HaCaT and skin fibroblast WS1 cells. Moreover, fenofibrate significantly decreased radiation-induced ROS and malondialdehyde (MDA) levels in electron beam irradiated skin tissues of rats. Mechanistically, the proximal promoter of fatty acid binding protein 4 (FABP4) harbored three binding sites of PPARα and fenofibrate stimulated the transcription of FABP4 in skin cells. FABP4 overexpression decreased radiation-induced ROS and γH2AX foci. FABP4 inhibitor BMS309403 abrogated the ROS-eliminating activity as well as the lipid-accumulating role of fenofibrate, indicating that FABP4 mediates the radioprotective role of fenofibrate. In addition, FABP4 overexpression significantly decreased radiation-induced oxidative damage in vivo. Conclusions: These results confirm that fenofibrate attenuated radiation-induced oxidative damage to the skin by stimulating FABP4.

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Section: Animal Studiesmentioning

confidence: 99%

Fenofibrate Attenuates Radiation-Induced Oxidative Damage to the Skin through Fatty Acid Binding Protein 4 (FABP4)

Sun¹,

Song²,

Sheng³

et al. 2022

Front. Biosci. (Landmark Ed)

Self Cite

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“…A 3-cm-thick piece of lead was used to shield the animals and localize the radiation field (3×4 cm). Irradiation was administered to the treatment area at a dose rate of 750 cGy/min using a 6-MeV electron beam accelerator (Clinac 2100EX, Varian Medical Systems) as we reported previously (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Animal Studiesmentioning

confidence: 99%

“…No animals were excluded from analysis. Skin reactions were graded at regular intervals from 1 (no damage) to 5 (severe damage) using the semiquantitative skin injury scale as previously described (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Animal Studiesmentioning

confidence: 99%

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

Xue

Tang

et al. 2021

Front. Oncol.

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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.

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“…In that study, done in a rat strain that has a propensity toward diet-induced obesity, researchers found that the levels of certain fatty acids were modified, with the coffee consumption presumed to play a role by altering the microbiome of the gut. The impact of certain dietary changes in the radiation response of both circulating blood [98] and irradiated skin [99] has also been noted. For example, in ex vivo irradiated blood samples from healthy donors who only modified their diet through increased consumption of tomato juice (known to contain free radical scavengers), there were changes noted in the levels of plasma reactive metabolite compounds and concentrations of lycopene and β-carotene.…”

Section: Extrinsic Factorsmentioning

confidence: 99%

Metabolomics in Radiation Biodosimetry: Current Approaches and Advances

et al. 2020

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Triage and medical intervention strategies for unanticipated exposure during a radiation incident benefit from the early, rapid and accurate assessment of dose level. Radiation exposure results in complex and persistent molecular and cellular responses that ultimately alter the levels of many biological markers, including the metabolomic phenotype. Metabolomics is an emerging field that promises the determination of radiation exposure by the qualitative and quantitative measurements of small molecules in a biological sample. This review highlights the current role of metabolomics in assessing radiation injury, as well as considerations for the diverse range of bioanalytical and sampling technologies that are being used to detect these changes. The authors also address the influence of the physiological status of an individual, the animal models studied, the technology and analysis employed in interrogating response to the radiation insult, and variables that factor into discovery and development of robust biomarker signatures. Furthermore, available databases for these studies have been reviewed, and existing regulatory guidance for metabolomics are discussed, with the ultimate goal of providing both context for this area of radiation research and the consideration of pathways for continued development.

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Ionizing radiation induces cutaneous lipid remolding and skin adipocytes confer protection against radiation-induced skin injury

Cited by 25 publications

References 36 publications

Fenofibrate Attenuates Radiation-Induced Oxidative Damage to the Skin through Fatty Acid Binding Protein 4 (FABP4)

Fenofibrate Attenuates Radiation-Induced Oxidative Damage to the Skin through Fatty Acid Binding Protein 4 (FABP4)

NF-E2-Related Factor 2 (Nrf2) Ameliorates Radiation-Induced Skin Injury

Metabolomics in Radiation Biodosimetry: Current Approaches and Advances

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