单核/巨噬细胞Matriptase糖基化活化uPA促进脂质合成调控放射性皮肤损伤的机制研究

放射性皮肤损伤机理不明，也缺乏有效的防治手段。皮肤脂质对于保持皮肤的屏障功能具有非常重要的作用，但其在辐射损伤中的作用及调控机制未见报道。我们前期通过二代测序发现电离辐射后皮肤组织中脂质合成与代谢相关基因表达显著下调。我们的前期研究及文献表明电离辐射引起大量单核/巨噬细胞向受照射皮肤组织迁移浸润，单核/巨噬细胞表面Matriptase可通过糖基化修饰激活尿激酶型纤溶酶原激活剂（uPA），促进皮肤细胞脂质的合成。本项目拟在前期研究基础上阐明电离辐射后浸润至皮肤的单核/巨噬细胞表面Matriptase通过糖基化修饰激活uPA/uPAR通路后促进微环境中皮肤脂质合成的分子机制，明确脂质合成在放射性皮肤损伤修复中的作用及调控机制。本项目有望从单核/巨噬细胞促进微环境中皮肤细胞脂质合成的角度对放射性皮肤损伤的修复机制有更深入的了解，为放射性皮肤损伤提供新的防治手段。

The molecular mechanism of radiation-induced skin injury remains unclear. Currently, no effective therapeutic countermeasures are available for patients with radiation-induced skin injury. Previous evidences have shown that lipids serving as a barrier play important roles in wound healing, however, their role in radiation-induced skin injury and the regulatory mechanism are still unknown. Documents and our preliminary studies showed that monocytes/macrophages could be infiltrated into the irradiated skin tissues, which activate urokinase-type plasminogen activator (uPA) through Matriptase on cell surface and promote lipid metabolism. Therefore, in this project, we will explore the mechanism of Matriptase on monocyte/macrophage in activation of uPA/uPAR pathway by glycosylation during lipids synthesis in the microenvironment of irradiated skin tissues. This project is likely to elucidate the role of lipid in wound repair of radiation-induced skin injury and its regulatory mechanism, which will provide novel approaches for prevention and treatment of radiation-induced skin injury.