title: Repulsive guidance molecule A suppresses angiogenesis.
abstract: The repulsive guidance molecule-a (RGMa) is a membrane-associated glycoprotein that has diverse functions in the developing and adult central nervous system. Here, we show that RGMa suppresses new blood vessel formation. Treatment of human umbilical artery endothelial cells (HUAEC) on Matrigel with recombinant RGMa inhibits vascular endothelial growth factor (VEGF)-induced and VEGF-independent tubular formation and migration. RGMa enhances adhesion presumably through dephosphorylation of focal adhesion kinase (FAK) at tyrosine-397. Neogenin, an RGMa receptor, in HUAEC is required for the effect of RGMa. In vivo Matrigel plug assay reveals that treatment with recombinant RGMa suppresses angiogenesis. Thus, we conclude that RGMa inhibits angiogenesis in vitro and in vivo suggesting that its manipulation would be an efficient therapeutic strategy for pro-angiogenic conditions.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 5 Sanbancho, Chiyoda-ku, Tokyo, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 5 Sanbancho, Chiyoda-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), 5 Sanbancho, Chiyoda-ku, Tokyo, Japan. Electronic address: yamashita@molneu.med.osaka-u.ac.jp.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042501:Angiogenic Proteins; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; C522183:RGMA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Angiogenesis; Focal adhesion kinase; HUAEC; Neogenin; RGM