长链非编码RNA WTAPP1对内皮祖细胞功能的调节机制及其在深静脉血栓中转化应用的实验研究

内皮祖细胞（EPC）在深静脉血栓形成（DVT）的再通中起着重要作用，但外周血中EPC含量较少且易受年龄等因素的影响，使其作用效果减弱，如何提高其归巢和成血管能力显得尤为重要。我们前期发现DVT患者EPC中lnc-WTAPP1表达降低，此lncRNA不仅与对细胞归巢和血管新生起重要作用的金属基质蛋白酶1（MMP1）在遗传学上相关，还与miR-9的表达呈负相关，同时后者也与MMP1相关。据此推测lnc-WTAPP1可能通过影响miR-9来调控MMP1表达进而提高EPC在血栓再通中的作用。本研究将①探明lnc-WTAPP1对EPC归巢及成血管能力的影响；②研究lnc-WTAPP1通过miR-9来调控MMP1的分子机制；③通过动物血栓模型解析EPC参与调控DVT转归过程中lnc-WTAAP1扮演的角色。该项目的完成将提出EPC归巢及成血管的新机制及为DVT的干细胞治疗及转归评价提供重要的理论依据。

Endothelial progenitor cell (EPC) plays an important role in the recanalization of deep vein thrombosis (DVT). But there are a few numbers of EPC in peripheral blood. Furthermore, EPC and its function are also confined by age and other risk factors, which will impair the roles of recanalizaion in DVT. Thus it is very important to improve the capacities of homing and angiogenesis. According to our previous study, we found that the expression of lncRNA WTAPP1 in EPC from DVT patients was lower than that from healthy donors. Metal Matrix Proteinase 1 (MMP1) was identified as the target gene of lncRNA WTAPP1. Besides, miR-9-5p also can target on MMP1 and expressed higher in the cells with lncRNA WTAPP1 siRNA. MMP1 plays an important role in the migration and angiogenesis. Thus, we suspected that lncRNA WTAPP1 could promote MMP1 expression through the regulation of MiR-9-5p, and further enhance the migration and angiogenesis of EPC. In this study, ①. We will find out the role of lncRNA WTAPP1 in homing and angiogenesis of EPC; ② identify the mechanisms of the regulation of MMP1 by lncRNA WTAPP1 through miR-9-5P; ③. Explore the role of lncRNA WTAPP1 in the assessment of DVT prognosis via animal model of thrombosis. This project will provide an important theoretical reference for stem cell treatment and prognosis evaluation of DVT.