title: Negative regulation of endothelial morphogenesis and angiogenesis by S1P2 receptor.
abstract: We speculated that the sphingosine-1-phosphate (S1P) receptor S1P(2), which uniquely inhibits cell migration, might mediate inhibitory effects on endothelial cell migration and angiogenesis, different from S1P(1) and S1P(3). Mouse vascular endothelial cells, which endogenously express S1P(2) and S1P(3), but not S1P(1), responded to S1P and epidermal growth factor (EGF) with stimulation of Rac, migration, and the formation of tube-like structures on the Matrigel. The S1P(3)-antagonist VPC-23019 abolished S1P-induced, G(i)-dependent Rac stimulation, cell migration, and tube formation, whereas the S1P(2)-antagonist JTE-013 enhanced these S1P-induced responses, suggesting that S1P(2) exerts inhibitory effects on endothelial Rac, migration, and angiogenesis. S1P(2) overexpression markedly augmented S1P-induced, G(i)-independent inhibition of EGF-induced migration and tube formation. Finally, the blockade of S1P(2) by JTE-013 potentiated S1P-induced stimulation of angiogenesis in vivo in the Matrigel implant assay. These observations indicate that in contrast to S1P(1) and S1P(3), S1P(2) negatively regulates endothelial morphogenesis and angiogenesis most likely through down-regulating Rac.
authors.affiliation: Department of Physiology, Graduate School of Medical Sciences, Kanazawa University, Ishikawa 920-8640, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Inoki
authors.forename: Noriko
authors.initials: N
authors.lastname: Takuwa
authors.forename: Naotoshi
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Takata
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.forename: Yoh
authors.initials: Y
authors.lastname: Takuwa
mesh_terms: D000818:Animals; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004727:Endothelium / Q000254:growth & development; D051379:Mice; D009024:Morphogenesis / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D049349:Receptors, Lysosphingolipid / Q000502:physiology*; D013268:Stimulation, Chemical; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000502:physiology
chemical_list: D049349:Receptors, Lysosphingolipid; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins