| Fang Shaofen,Feng Yang,Zhang Qi,et al.Study on the role of RNA m6A methyltransferase in promoting ultraviolet B radiation-induced skin injury[J].Chinese Journal of Radiological Medicine and Protection,2024,44(7):555-561 |
| Study on the role of RNA m6A methyltransferase in promoting ultraviolet B radiation-induced skin injury |
| Received:January 08, 2024 |
| DOI：10.3760/cma.j.cn112271-20240108-00006 |
| KeyWords:Ultraviolet B Radiation-induced skin injury METTL14 RNA m6A methylation |
| FundProject:国家自然科学基金(U1967220,81872552,12075165);国家重点研发计划项目(2022YFC2503700,2022YFC2503703) |
| Author Name | Affiliation | E-mail | | Fang Shaofen | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Feng Yang | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Zhang Qi | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Zhu Wei | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Jiao Yang | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Cao Jianping | State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | jpcao@suda.edu.cn |
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| Abstract:: |
| Objective To investigate the regulatory role of RNA m6A methyltransferase (METTL14) in ultraviolet B (UVB) radiation-induced skin injury, and to preliminarily explore the potential of targeted inhibition of METTL14 for treating UVB-induced skin injury. Methods A UVB radiation-induced skin injury model was established by exposing C57BL/6J mice to 150 mJ/cm2 UVB, and was assessed and scored with HE staining and Masson staining. UVB radiation-induced cell injury models were established by exposing human immortalized keratinocytes (HaCaT) and human skin fibroblasts (WS1) to 10 and 30 mJ/cm2 UVB, respectively. The m6A levels in the mouse skin and cell models after UVB exposure were quantified by colorimetric assay, and m6A-related enzymes in cells were measured by Western blot. HaCaT and WS1 cell lines overexpressing METTL14 were constructed using recombinant adenoviral vectors, and the overexpression effects were tested by Western blot. The METTL14 overexpression cells were examined for their m6A levels, proliferative abilities after UVB exposure (by clone formation assay), and changes in apoptosis (by flow cytometry). The model mice with UVB-induced skin injury in the treatment groups received subcutaneous injection of the METTL14 inhibitor S-adenosylhomocysteine (SAH) solution (1 mg/kg, 5 mg/kg) twice consecutively before and after irradiation; and the mice were assessed and scored for skin injury with HE staining and Masson staining. Results On the 4th day after 150 mJ/cm2 UVB irradiation, the mice showed remarkable skin injury, pathologically featuring inflammatory infiltration, tissue structure disorganization, and collagen fiber degradation, reaching the maximum score; and the m6A level in the skin was significantly downregulated (t = 3.07, P ＜ 0.05). At 24 h after 10 and 30 mJ/cm2 irradiation, HaCaT and WS1 cells showed significantly reduced survival rates (t = 7.64, 7.15, P ＜ 0.05), significantly downregulated m6A levels (t = 4.78, 4.36, P <0.05), and significantly time-dependent downregulation of METTL14 protein expression (t = 6.39, 4.76, P ＜ 0.05). In HaCaT and WS1 cells, METTL14 overexpression significantly up-regulated m6A levels (t = 7.66, 3.67, P ＜ 0.05), significantly inhibited the clone-forming ability of cells after UVB irradiation (t = 6.29, 3.84, P ＜ 0.05), and significantly increased the rate of cell apoptosis (t = 3.48, 9.54, P ＜ 0.05). Compared with those in the normal saline group, the model mice with UVB-induced skin injury in the SAH treatment group (5 mg/kg) showed significantly decreased pathological scores of skin injury (t = 3.21, 4.27, 5.81, P ＜ 0.05), with milder inflammatory infiltration, more orderly tissue structure, and less collagen fiber degradation. Conclusions METTL14 can increase the sensitivity of skin cells to UVB radiation, and targeted inhibition of METTL14 can effectively alleviate UVB radiation-induced skin injury, which may be a potential new target for the treatment of UVB radiation-induced skin injury. |
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