血小板与内皮细胞（EC）通过信息交流共同维持血液循环的功能稳态。脓毒症时，血管内皮严重受损，引起弥散性血管内凝血（DIC）。尽管DIC长期引起关注，但血栓形成后，受损内皮在与循环血液完全隔离的情况下如何完成修复过程至今未明。我们前期报道脂多糖（LPS）可诱导SCUBE1与内皮结合；进一步实验发现，脓毒症时血栓中SCUBE1丰富，血浆中游离的SCUBE1显著升高；蛋白酶Furin可在体外通过RRGR位点对SCUBE1进行切割。基于上述发现，我们提出假说：脓毒症血栓形成导致局部缺氧，SCUBE1上二硫键打开，暴露其间隔区的RRGR基序，Furin通过识别该基序而对SCUBE1切割，形成具有活性的功能片段，从而促进EC增殖、迁移，使损伤内皮得以修复。本项目拟利用小鼠基因敲除（入）、蛋白质组学技术以及细胞生物学和分子生物学策略验证上述假说，以期为脓毒症内皮损伤修复提供新理论，并为治疗提供新思路。

Platelets and endothelial cells (ECs) maintain the homeostasis of blood circulation through information exchange. In sepsis, the vascular endothelium is severely damaged, leading to disseminated intravascular coagulation (DIC). Although DIC has long attracted attention, it is not clear how the damaged endothelium complete the repair process after thrombosis in complete isolation from the circulating blood. We previously reported that lipopolysaccharide (LPS) can induce SCUBE1 binding with endothelium. Further experiments showed that SCUBE1 was abundant in thrombus and significantly increased in plasma as a free form during sepsis. The protease Furin can cut SCUBE1 in vitro by RRXR site. Based on these findings, we raise the hypothesis that local hypoxia resulted from sepsis thrombi formation, the disulfide bond on SCUBE1 was opened, and the RRGR motif in its spacer region was exposed. By identifying this motif, Furin cuts SCUBE1 leading the formation of functional fragments with activity, thus promoting the proliferation and migration of ECs and repairing the damaged endothelium. This project is designed to use the technologies of mouse gene knockout and knockin, proteomics technology and strategies of cell biology and molecular biology to verify the above hypothesis, so as to provide a new theory for endothelial repair of sepsis and novel ideas for clinical therapy.