X. Yuji; Suzhou University Affiliated Second Hospital, Soochow, Jiangsu, China
Purpose/Objective(s): This project proposes to investigate the mechanism of fatty acids affecting cellular ferroptosis on radiation-induced skin injury through regulation of the stearyl CoA desaturase (SCD) at the molecular, cellular and in vivo levels, which is important for clarifying the pathological role of SCD in radiation-induced skin injury and is expected to provide new prevention and treatment strategies for radiation-induced skin injury. Materials/
Methods: Using a co-culture model of skin cells and adipocytes, as well as an animal model of radiation-induced skin injury, to detect changes in skin cell proliferation, clone formation, and skin structure after ionizing radiation, and to clarify the effect of fatty acids on radiation-induced skin injury; And in vivo validation of the effect of fatty acids on radiation-induced skin injury was conducted using a rat radiation-induced skin injury model. Preprocess skin cells with ferroptosis inhibitors to obtain ferroptosis resistant cell lines, and detect the changes in cell clone formation after ionizing radiation to clarify the relationship between ferroptosis and skin cell radiation resistance. Using different types of fatty acids to treat skin cells, using tools such as ferroptosis related antibodies and lipid peroxidation fluorescent probes, to clarify the effect of fatty acids on ferroptosis in skin cells after ionizing radiation. In addition, the skin gene chips before and after fatty acid treatment were analyzed to screen for potential mechanisms of ferroptosis regulating radiation-induced skin damage. Results: Compared with the control group, adipocytes can cause radiation resistance of skin cells or tissues to X-rays both in vivo and in vitro; Skin cells can freely consume free fatty acids derived from adipocytes; Ferroptosis occurs in skin cells after ionizing radiation, and lipid peroxidation levels are inhibited by fatty acids; Analysis of skin gene chips before and after fatty acid treatment revealed that SCD gene was significantly downregulated after ionizing radiation, while the SCD gene remained upregulated in the fatty acid treatment group under ionizing radiation and was significantly correlated with lipid peroxidation. The mechanism involved may be related to the regulation of monounsaturated fatty acid (MUFAs) synthesis pathways. Conclusion: Fatty acids can play a protective role against radiation induced skin damage, and their mechanism may be related to the regulation of the key enzyme SCD in the MUFAs synthesis pathway by fatty acids, which inhibits ferroptosis.
