title: Inactivation of EphA2 promotes tight junction formation and impairs angiogenesis in brain endothelial cells.
abstract: Eph receptor tyrosine kinases and ephrin ligands participate in the regulation of a wide variety of biological processes, such as axon guidance, synaptic plasticity, angiogenesis, and tumorigenesis. The role of Eph receptors and ephrin ligands in brain endothelial cells remains unknown. Here, we examined the expression profile of EphA receptors and ephrin-A ligands in human brain microvascular endothelial cell line (HBMEC). Our results showed that multiple EphA receptors and ephrin-A ligands are expressed in HBMEC. We found that the phosphorylation of EphA2, but not other EphA receptors, was significantly increased in HBMEC treated with recombinant ephrin-A1/Fc. Meanwhile, elevated EphA2 phosphorylation was accompanied by disassembly of tight junctions in HBMEC. Furthermore, EphA2 RNAi in HBMEC could promote tight junction formation and prevent the ephrin-A1-induced tight junction disruption. Also, when a kinase-inactive mutant of EphA2 (EphA2-K646M) was expressed in HBMEC, the tight junction was enhanced and the ephrin-A1-induced tight junction disruption was blocked. In addition, EphA2 RNAi and expression of EphA2-K646M in HBMEC inhibited in vitro cell migration and angiogenesis of HBMEC. These data indicated an important role of EphA2 in regulating both tight junction formation and angiogenesis in brain endothelial cells.
authors: Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University,92 Bei Er Road, Heping District, Shenyang 110001, China.
authors: Na
authors: N
authors: Zhou
authors: Wei-Dong
authors: WD
authors: Zhao
authors: Dong-Xin
authors: DX
authors: Liu
authors: Yue
authors: Y
authors: Liang
authors: Wen-Gang
authors: WG
authors: Fang
authors: Bo
authors: B
authors: Li
authors: Yu-Hua
authors: YH
authors: Chen
mesh_terms: D001921:Brain / Q000098:blood supply* / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D010539:Permeability; D010766:Phosphorylation; D034622:RNA Interference; D036104:Receptor, EphA2 / Q000378:metabolism* / Q000502:physiology; D013347:Subcellular Fractions; D019108:Tight Junctions / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D008024:Ligands; D036104:Receptor, EphA2