本项目假设ERM蛋白的苏氨酸磷酸化可以激活内皮细胞，促进tip cells的形成，加速内皮细胞的迁移、增殖和毛细血管成管，促进血管新生，导致血管新生的发生发展。本研究将借助免疫细胞化学等技术，利用siRNA、构建激活型或抑制型突变体等方法，通过观察视网膜内皮细胞的尖细胞形成、迁移、增殖和成管等指标，探讨ERM蛋白在血管新生过程中的作用；并观察晚期糖基化终产物（AGE）干预对血管新生过程的影响及其ERM蛋白在其中的作用，以探讨糖尿病增生性视网膜病的发病机制；鉴于血管新生不足导致的糖尿病皮肤损伤修复障碍可能是糖尿病足发病的原因，本研究还将以皮肤微血管内皮细胞为另一研究对象，观察两种组织的内皮细胞在相同刺激条件下的激活、迁移和增殖并进行比较，进一步阐明ERM在其中的作用，并在组织和整体水平验证。旨在揭示ERM蛋白对血管新生的影响，探讨糖尿病增生性血管病发病的下游分子机制，为临床诊治提供新的思路。

It is proposed that advanced glycation end products (AGEs) is involved in the development of diabetic angiogenesis by inducing the threonine phosphorylation of erzin, radixin, and moesin (ERM proteins). The phosphorylation of ERM will mediates the formation of endothelial tip cells, and the migration, proliferation, and tubulogenesis of endothelial cells, leading to the pathological angiogenesis. Using timelapse technique of confocal microscope and other cellular and molecular biological methods such as siRNA and mutant constructs, this proposal focuses on exploring the effects of ERM protein on AGE-induced angiogenesis by observing the formation of endothelial tip cells, and the migration, proliferation, and tubulogenesis of endothelial cells. The in vivo animal model will be used to validate the effects of ERM on cellular level. This proposal aims to elucidate the involvement of ERM protein in the progress of angiogenesis and the mechanism of AGE-induced diabetic proliferative microangiopathy.