Research Article

ERM复合物,糖尿病诱导血管渗漏的治疗靶点

卷 29, 期 12, 2022

发表于: 17 August, 2021

页: [2189 - 2199] 页: 11

弟呕挨: 10.2174/0929867328666210526114417

摘要

背景:Ezrin,radixin和moesin(ERM复合物)直接与膜蛋白相互作用,调节它们与肌动蛋白丝的附着。ERM蛋白活化可改变细胞骨架组织并改变内皮屏障功能,从而有利于血管渗漏。然而,关于ERM蛋白在糖尿病视网膜病变(DR)中的作用知之甚少。目的:探讨DB/db小鼠中ERM复合物是否存在过表达及其主要调节因子。 方法:分析9只雄性db/db小鼠和9只14周龄雄性db/+小鼠。通过免疫印迹和免疫组织化学评估ERM蛋白。血管渗漏由埃文斯蓝法确定。为了评估ERM调节,在含有5.5mM D-葡萄糖(模仿生理条件)和25 mM D-葡萄糖(模仿糖尿病患者发生的高血糖)的培养基中培养HREC。此外,用TNF-α,IL-1β或VEGF治疗被添加到高血糖条件下。通过RT-PCR定量ERM蛋白的表达。通过测量FITC-葡聚糖的运动来评估细胞通透性。 结果:与非糖尿病小鼠相比,观察到糖尿病小鼠ERM显着增加。单独使用高血糖状况对ERM表达没有任何影响。然而,TNF-α和IL-1β诱导ERM蛋白的显着增加。 结论:糖尿病诱导的ERM蛋白增加可能是血管渗漏的机制之一,可作为治疗靶点。此外,糖尿病对ERM复合物的上调是由炎症介质引起的,而不是由高葡萄糖本身引起的。

关键词: 依嗪素,萝卜毒素,蛋白酶,糖尿病视网膜病变,视网膜通透性,db / db小鼠,人视网膜内皮细胞。

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