静脉畸形是一种常见于小儿的先天性血管发育异常性疾病。静脉畸形中的血管处于非稳定状态，且细胞外基质降解异常是该过程中的关键事件。本项目前期研究证实静脉畸形内皮细胞可分泌大量富含基质金属蛋白酶的外泌体，且后者具有明显的细胞外基质降解能力。此外，我们的研究结果还表明静脉畸形内皮细胞中异常活化的Akt信号通路可能通过调控Rabin8/Rab8途径促进外泌体分泌。本项目旨在进一步探究：（1）外泌体分泌异常在静脉畸形细胞外基质降解中的作用和机制；（2）Rabin8/Rab8对静脉畸形内皮细胞外泌体分泌的调控作用和分子机制；（3）Akt通过磷酸化Rabin8调控Rab8活性的作用和机制。本项目不仅有助于进一步阐明静脉畸形的发病机制，还可能为研究血管稳态的调控机制提供新的思路。

Venous malformations (VMs) are congenital vascular anomalies. Previous studies have revealed that the vessels in VM are in an unstable state, which is closely associated with the excessive degradation of extracellular matrix (ECM). Our preliminary results showed that endothelial cells derived from VM patients (VMECs) secreted an increased level of exosomes carrying abundant matrix metalloproteinases (MMPs) on their surface. These exosomes showed a great ability in ECM degradation. Our results also suggested that the activated Akt in VMECs likely promotes exosome secretion through its regulation of the Rabin8/Rab8 pathway. The aim of this project is to further explore: (1) the role of exosome secretion in the degradation of ECM in VMs; (2) the regulation and molecular mechanism of Rabin8/Rab8 on exosome secretion in VMECs; (3) the role and mechanism about Akt regulates Rab8 activity by phosphorylating Rabin8. This project will not only further elucidate the pathogenesis of VM, and would also shed new light on the studies of the regulatory mechanism of vascular homeostasis.