Advanced glycation end products induce moesin phosphorylation in murine retinal endothelium
Advanced glycation end products induce moesin phosphorylation in murine retinal endothelium
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DOI：
10.1007/s00592-011-0267-z
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Huang, Qiaobing
中科院分区：
文献类型：
--
作者：
Wang, Lingjun;Li, Qiaoqin;Huang, Qiaobing
血管通透性增加是糖尿病视网膜病变发展过程中最重要的病理事件。晚期糖基化终末产物（AGEs）的沉积在糖尿病的发生过程中起着至关重要的作用。本研究旨在探讨 moesin 及其潜在信号转导在 AGE 修饰小鼠血清白蛋白 (AGE-MSA) 诱导的视网膜血管通透性过高中的作用。雌性C57BL/6小鼠通过连续7天腹腔内施用AGE-MSA来产生AGE处理模型。通过伊文思蓝渗漏测定对内部血视网膜屏障进行定量。通过荧光探针染色观察视网膜脉管系统中的内皮F-肌动蛋白细胞骨架。采用RT-PCR和Western blotting检测视网膜血管中moesin的表达和磷酸化。进一步研究探讨 Rho 激酶 (ROCK) 和 p38 MAPK 通路对 moesin 参与 AGE 诱导的视网膜血管高通透性反应的影响。 AGE-MSA 治疗显着增加了视网膜微血管的通透性，并诱导视网膜血管内皮细胞中 F-肌动蛋白的解体。施用 AGE 后，视网膜血管中 moesin 的苏氨酸 (T558) 磷酸化显着增强。通过抑制 ROCK 和 p38 MAPK 可以减弱 moesin 的磷酸化，同时这种治疗还可以防止内部血-视网膜屏障的功能障碍以及视网膜血管内皮细胞中 F-肌动蛋白的重组。这些结果表明，moesin 参与 AGE 诱导的视网膜血管内皮功能障碍，并且 moesin 的磷酸化是通过 ROCK 和 p38 MAPK 激活触发的。
Increase in vascular permeability is the most important pathological event during the development of diabetic retinopathy. Deposition of advanced glycation end products (AGEs) plays a crucial role in the process of diabetes. This study was to investigate the role of moesin and its underlying signal transduction in retinal vascular hyper-permeability induced by AGE-modified mouse serum albumin (AGE-MSA). Female C57BL/6 mice were used to produce an AGE-treated model by intraperitoneal administration of AGE-MSA for seven consecutive days. The inner blood-retinal barrier was quantified by Evans blue leakage assay. Endothelial F-actin cytoskeleton in retinal vasculature was visualized by fluorescence probe staining. The expression and phosphorylation of moesin in retinal vessels were detected by RT-PCR and western blotting. Further studies were performed to explore the effects of Rho kinase (ROCK) and p38 MAPK pathway on the involvement of moesin in AGE-induced retinal vascular hyper-permeability response. Treatment with AGE-MSA significantly increased the permeability of the retinal microvessels and induced the disorganization of F-actin in retinal vascular endothelial cells. The threonine (T558) phosphorylation of moesin in retinal vessels was enhanced remarkably after AGE administration. The phosphorylation of moesin was attenuated by inhibitions of ROCK and p38 MAPK, while this treatment also prevented the dysfunction of inner blood-retinal barrier and the reorganization of F-actin in retinal vascular endothelial cells. These results demonstrate that moesin is involved in AGE-induced retinal vascular endothelial dysfunction and the phosphorylation of moesin is triggered via ROCK and p38 MAPK activation.