颅内动脉瘤形成机制仍不清楚，本项目在申请人前期发现VE-cadherin磷酸化在其中发挥重要作用和对VE-cadherin磷酸化调控相关因子进行系统分析的基础上，结合p120ctn不仅调控VE-cadherin磷酸化，且能与转录抑制因子kaiso结合参与内皮细胞核内靶基因调控的科研实践，分析与颅内动脉瘤形成相关基因的启动子区域，发现MMP-2启动子系列里含有两个Kaiso能识别的系列，提出VE-Cadherin 磷酸化介导的P120ctn、Kaiso和MMP-2信号通路与颅内动脉瘤形成机制相关的假说。拟应用抑制剂、基因干扰和萤火虫酶检测等技术，通过体内和体外实验，探讨VE-cadherin磷酸化诱导p120ctn，kaiso和MMP-2信号通路在动脉瘤形成中的作用及调控机制，为探明颅内动脉瘤形成机制奠定实验基础和理论依据。

The formation mechanism of intracranial aneurysm is still unclear. It was confirmed by our previous study that vascular endothelial injury initiated by VE-Cadherin phosphorylation play an important role in the formation of intracranial aneurysms. The association of VE-Cadherin phosphorylation with P120 catenin shows that VE-Cadherin phosphorylation can regulate P120 catenin function. It has been reported that p120ctn can bind directly with a transcription factor, Kaiso, implicating a possible function as a co-factor for this transcription factor. Worthy of investigation, we found Matrix Metalloproteinase-2(MMP-2), a member of the MMPs family which are involved in proteolytic modeling of the extracelluar matrix, possess two conserved copies of the core sequence-specific Kaiso site. Probably, MMP-2 is the target gene of Kaiso.MMP-2 has been showed to play a critical role in the formation of intracranial aneurysms, however the regulation of MMP-2 gene in endothelial cell is not very clear yet. In this study,we are about to explore the relationship between transcription of MMP-2 and the P120 catenin -Kaiso complex and try to test the hypothesis that P120 catenin, Kaiso,and MMP-2 signal initiated by VE-Cadherin phosphorylation is involved in the aneurysmal formation.