病理性血管新生具有血管新生过度但成熟不足的特征。本实验室已有的研究证明ERM蛋白moesin的过度磷酸化可促进血管新生，并伴随明显的成熟不足；晚期糖基化终产物（AGEs）通过磷酸化moesin而导致血管新生过度；文献和预实验提示磷酸化moesin对CD44有明显簇集作用。课题将在细胞、组织和整体水平，从moesin及其磷酸化与CD44相互作用的角度，观察moesin及其磷酸化与CD44相互作用对内皮细胞钙依赖性粘附素（VE-cadherin）表达以及细胞间粘附连接形成的影响和机制；观察moesin及其磷酸化与CD44相互作用对内皮细胞募集周细胞、周细胞在新生血管的覆盖率、以及基底膜形成的影响，从而探讨病理性血管新生成熟不足的机制，并证明糖尿病血管并发症的发生过程中，AGEs通过引起moesin的磷酸化而簇集CD44，导致新生血管的成熟不足。

Excessive angiogenesis, as well as neovessel immaturation are important characteristics of various pathological processes such as the atherosclerosis and proliferative diabetic retinopathy. Our previous studies have shown that the phosphorylation of ERM protein moesin can promote angiogenesis, accompanying with obvious neovessel immaturation. Advanced glycation endproducts (AGEs) can lead to excessive angiogenesis by phosphorylating moesin. This proposal will elucidate the effects of moesin and its phosphorylation on clustering CD44 in regulation of expression and cellular distribution of VE-cadherin in maturity of neovessel. This proposal will investigate the effect of interaction of moesin/p-moesin and CD44 on vascular pericyte coverage and the formation of heterogeneou adherent junction between endothelial cell and pericytes, as well as the formation of basement membrane in neovessels. This proposal will also explore the characteristics and mechanism of AGE-mediated neovessel immaturation by using cytologic, particularly histologic three-dimensional culture techniques. This study aims to explore the mechanisms of neovessel immaturation in pathological angiogenesis, and to prove that AGEs could induce excessive neovascularization, as well as insufficient neovessel maturation by phosphorylating ERM protein moesin.