| Jiang Fengdi,Liu Yifan,Ou Xiaolan,et al.Study on the protective effects of fenofibrate against UVB-induced skin damage and its mechanisms[J].Chinese Journal of Radiological Medicine and Protection,2026,46(7):641-649 |
| Study on the protective effects of fenofibrate against UVB-induced skin damage and its mechanisms |
| Received:August 12, 2025 |
| DOI：10.3760/cma.j.cn112271-20250812-00293 |
| KeyWords:Ultraviolet B Fenofibrate Peroxisome proliferator-activated receptor α Photodamage Lipidomics |
| FundProject:西藏自治区科技计划项目重点研发计划(XZ202501ZY0131);天府锦城实验室(前沿医学中心)成果转化项目(2025ZH006);四川省区域创新合作项目(2026YFHZ0164) |
| Author Name | Affiliation | E-mail | | Jiang Fengdi | Department of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China | | | Liu Yifan | Department of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Tianfu Jincheng Laboratory (Frontier Medical Center), Chengdu 610093, China | | | Ou Xiaolan | Department of Plastic and Burn Surgery, Nuclear Industry 416 Hospital, Chengdu 610051, China | | | Guo Linfen | Department of Burn and Plastic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China | | | Wang Jiajia | School of Medicine, Tibet University, Lhasa 850000, China | | | Xiong Hai | School of Medicine, Tibet University, Lhasa 850000, China | | | Yu Daojiang | Department of Plastic and Burn Surgery, Nuclear Industry 416 Hospital, Chengdu 610051, China | | | Zhang Shuyu | Department of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China
Tianfu Jincheng Laboratory (Frontier Medical Center), Chengdu 610093, China | zhang.shuyu@hotmail.com |
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| Abstract:: |
| Objective To investigate the effects of the peroxisome proliferator-activated receptor α agonist fenofibrate on ultraviolet B (UVB)-induced skin damage and its underlying molecular mechanisms. Methods Twenty-five male C57BL/6J wild-type mice aged 6-8 weeks, a skin damage model was established by a single 2 J/cm2 UVB irradiation. The mice were randomly divided into a blank control group, a vehicle control group, a fenofibrate group, a saroglitazar group, and a GW6471 group, with 5 mice in each group. The corresponding agents were injected subcutaneously immediately after irradiation, and skin damage scores and wound area measurements were used to evaluate skin damage from 0 to 36 d post-irradiation. In addition, mice of the same strain were divided into a negative control group, a UVB irradiation group, a UVB+DMSO group, and a UVB+fenofibrate group. Skin tissue was collected at 4 d post-irradiation for lipid metabolomics analysis using liquid chromatography-tandem mass spectrometry. Human mature adipocytes were treated with DMSO, fenofibrate, saroglitazar, or GW6471 for 24 h, the culture medium was replaced with fresh medium, the incubation was continued for another 24 h, and the adipocyte-conditioned medium was collected. The above drugs or corresponding conditioned media were added to human immortalized keratinocytes (HaCaT cells), respectively. Flow cytometry was used to determine the apoptosis rate after UVB irradiation, the colony formation assay was used to assess the cell proliferation ability, and the cell scratch assay was used to evaluate the cell migration ability. Results Compared with the control group, the skin damage score of mice in the fenofibrate group decreased after UVB irradiation at 36 d (t=5.17, P<0.05). Compared with the apoptosis rate of (42.15±0.52)% in the DMSO group irradiated with 5 mJ/cm2 UVB, the apoptosis rate of HaCaT cells in the fenofibrate group irradiated with 5 mJ/cm2 UVB decreased to (34.56±0.50)% (t=22.42, P<0.05). Compared with the colony formation rate of (10.50±0.54)% in the DMSO group irradiated with 5 mJ/cm2 UVB, the colony formation rate of HaCaT cells in the fenofibrate group irradiated with 5 mJ/cm2 UVB increased to (23.35±1.07)% (t=14.30, P<0.05). Compared with the cell migration rate of (23.51±1.02)% in the Mock group, the cell migration rate in the fenofibrate group at 24 h increased to (28.46±1.28)% (t=22.84, P<0.05). Lipidomic profiling revealed that fenofibrate significantly altered various lipids in the skin after UVB irradiation, including the up-regulation of lipids such as OAHFA(40∶6), PA(34∶4e), and TG(16∶0e/16∶0/22∶6), and the down-regulation of TG(14∶0/18∶2/22∶6), PG(28∶0/16∶0), and Cer(d17∶0/24∶0). Conclusions Fenofibrate can significantly alleviate UVB-induced skin damage through multiple mechanisms, such as reducing skin damage, promoting wound healing, enhancing anti-apoptotic capacity of cells, and regulating disordered lipid metabolism in the skin. |
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