有效防治放射性肠损伤对于肿瘤放疗及应对核事故等具有重要意义。铁是人体必需的微量元素，但细胞中过量的铁沉积会引起严重的细胞毒性。Matriptase-2是高表达于肝脏的II型跨膜丝氨酸蛋白酶家族成员，可调节铁调素分泌影响铁离子代谢。肝脏Matriptase-2对放射性肠损伤的影响尚不清楚。本项目组前期发现电离辐射可抑制肝脏中Matriptase-2糖基化，引起分泌的铁调素增加，抑制肠上皮细胞中膜铁转运蛋白（ferroportin），引起铁沉积。本项目拟在前期研究基础上通过多种分子生物学手段及小鼠动物模型进一步探索 1）电离辐射抑制Matriptase-2糖基化后对铁调素及细胞铁离子稳态的影响；2）肝脏分泌的铁调素调控小肠上皮细胞中铁离子转运对电离辐射引起的损伤的影响。本项目可望从肝脏Matriptase-2调控肠道铁离子转运的角度揭示放射性肠损伤的新机制，为这一疾病的治疗提供新的靶点和策略。

Effective prevention and treatment of radiation-induced intestinal injury is of great significance for tumor radiotherapy and nuclear accident. Iron is essential for vertebrates, however, excessive amounts of iron in cells cause severe cytotoxicity. Matriptase-2 is a member of the type-II transmembrane serine protease family, which can regulate iron metabolism by hepcidin. Whether hepatic Matriptase-2 affects radiation-induced intestinal injury is not clear. In our preliminary study, we found that ionizing radiation could reduce the N-glycosylation of Matriptase-2 in liver, which could induce the secretion of hepcidin. Increased hepcidin inhibited the ferroportin activity and induced the accumulation of iron in interstinal epithelial cells. This project will use various molecular biology methods and mice model to further explore 1) The effect of the N-glycosylation of Matriptase-2 after ionizing radiation on hepcidin activation and iron homeostasis; 2) The effect of iron transportation regulated by hepcidin on radiation-induced intestinal injury. This project is expected to reveal the new mechanism of intestinal injury induced by ionizing radiation from the perspective of iron ion transportation regulated by hepatic Matriptase-2 and to provide new targets and strategies for the treatment of radiation-induced intestinal injury.