Hepsin属于Ⅱ型跨膜丝氨酸蛋白酶（TTSPs），在机体的肝组织中高表达。离体试验表明hepsin可以通过裂解底物在细胞信号转导和肿瘤发生发展中发挥重要作用；在体实验确认hepsin能够剪切uromodulin，在肾脏功能和相关疾病进展中发挥关键作用。我们最近报道hepsin在人和小鼠肝细胞中可以促进细胞因子IL-6和补体C3的分泌，参与机体的免疫应答。但是hepsin酶原激活的机制和在肝脏中的生理底物一直未见报道。本项目拟应用分子生物学、细胞生物学及蛋白质组学等手段深入研究hepsin的酶原激活机制和在肿瘤进程中发挥的重要作用，同时筛选鉴定hepsin在肝脏中的生理底物，以期揭示hepsin的生理病理功能和调控的具体信号机制，在此基础上完善以TTSPs家族分子为中心的信号转导及功能网络。

Hepsin, a type II transmembrane serine protease, is expressed in most tissues, with its highest levels in liver. In vitro studies suggest altered signaling induced by hepsin-mediated cleavage and activation of macromolecular substrates is required for invasion, migration and tissue diffusion of tumor. In vivo study revealed that hepsin mediated urinary secretion and polymerisation of Zona Pellucida domain protein uromodulin. It is exclusively produced by renal epithelial cells and it plays key roles in kidney function and disease. We found that hepsin promotes C3 production by inducing IL-6 secretion in hepatocytes and involved the immune response of organism. However, the mechanism of zymogen activation and physiological substrate(s) of the hepsin have not been unambiguously defined. On the basis of our findings，focusing on the mechanism and physiological substrate(s), we will deeply investigate the hepsin function by molecular biology and cell biology methods.