title: A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice.
abstract: Interactions between astrocytes and endothelial cells (ECs) are crucial for retinal vascular formation. Astrocytes induce migration and proliferation of ECs via their production of vascular endothelial growth factor (VEGF) and, conversely, ECs induce maturation of astrocytes possibly by the secretion of leukemia inhibitory factor (LIF). Together with the maturation of astrocytes, this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production in ECs are unclear. Here we show that apelin, a ligand for the endothelial receptor APJ, induces maturation of astrocytes mediated by the production of LIF from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis; however, aberrant overgrowth of endothelial networks with immature astrocyte overgrowth was induced. When ECs were stimulated with apelin, LIF expression was upregulated and intraocular injection of LIF into APJ-deficient mice suppressed EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in the maturation process of retinal angiogenesis.
authors.affiliation: Department of Signal Transduction, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakimoto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Naito
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kamei
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sakaguchi
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Goda
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Fukamizu
authors.forename: Kohji
authors.initials: K
authors.lastname: Nishida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
mesh_terms: D054392:Adipokines; D000818:Animals; D000073861:Apelin; D000075244:Apelin Receptors; D001253:Astrocytes / Q000166:cytology*; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012160:Retina / Q000473:pathology
chemical_list: C115436:APLN protein, human; D054392:Adipokines; D000073861:Apelin; D000075244:Apelin Receptors; C402826:Apln protein, mouse; C491285:Aplnr protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053605:Leukemia Inhibitory Factor; D008024:Ligands; D043562:Receptors, G-Protein-Coupled