title: Role of Moesin in Advanced Glycation End Products-Induced Angiogenesis of Human Umbilical Vein Endothelial Cells.
abstract: Disorders of angiogenesis are related to microangiopathies during the development of diabetic vascular complications, but the effect of advanced glycation end products (AGEs) on angiogenesis and the mechanism has not been completely unveiled. We previous demonstrated that moesin belonging to the ezrin-radixin-moesin (ERM) protein family protein played a critical role in AGE-induced hyper-permeability in human umbilical vein endothelial cells (HUVECs). Here, we investigated the impact of moesin on AGE-induced HUVEC proliferation, migration, and tubulogenesis. Silencing of moesin decreased cell motility and tube formation but not cell proliferation. It also attenuated cellular F-actin reassembly. Further, phosphorylation of threonine at the 558 amino acid residue (Thr 558) in moesin suppressed AGE-induced HUVEC proliferation, migration, and tube formation, while the activating mutation of moesin at Thr 558 enhanced HUVEC angiogenesis. Further, the inhibition of either RhoA activity by adenovirus or ROCK activation with inhibitor Y27632 decreased AGE-induced moesin phosphorylation and subsequently suppressed HUVEC angiogenesis. These results indicate that the Thr 558 phosphorylation in moesin mediates endothelial angiogenesis. AGEs promoted HUVEC angiogenesis by inducing moesin phosphorylation via RhoA/ROCK pathway.
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Aihui
authors.initials: A
authors.lastname: Fan
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Lixian
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Xuliang
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pathophysiology, Key Lab for Shock and Microcirculation Research, Southern Medical University, Guangzhou, 510515, P. R. China.
authors.forename: Qiaobing
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D019943:Amino Acid Substitution; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D020868:Gene Silencing; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic; D010766:Phosphorylation; D017354:Point Mutation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
chemical_list: D000199:Actins; D017127:Glycation End Products, Advanced; D008840:Microfilament Proteins; D050505:Mutant Proteins; C071058:moesin