title: Advanced glycation end products induce moesin phosphorylation in murine retinal endothelium.
abstract: 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.
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Tonghe, Guangzhou, People's Republic of China.
authors.forename: Lingjun
authors.initials: L
authors.lastname: Wang
authors.forename: Qiaoqin
authors.initials: Q
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Du
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Xuliang
authors.initials: X
authors.lastname: Huang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Guo
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology; D054460:rho-Associated Kinases / Q000378:metabolism / Q000502:physiology
chemical_list: D017127:Glycation End Products, Advanced; D008840:Microfilament Proteins; C071058:moesin; D011494:Protein Kinases; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases