A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice

Susumu Sakimoto, Hiroyasu Kidoya, Hisamichi Naito, Motohiro Kamei, Hirokazu Sakaguchi, Nobuhito Goda, Akiyoshi Fukamizu, Kohji Nishida, Nobuyuki Takakura

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1327-1335
    Number of pages9
    JournalDevelopment
    Volume139
    Issue number7
    DOIs
    Publication statusPublished - 2012 Apr 1

    Fingerprint

    Astrocytes
    Leukemia Inhibitory Factor
    Endothelial Cells
    Intraocular Injections
    Retinal Vessels
    Vascular Endothelial Growth Factor A
    Ligands

    Keywords

    • Apelin
    • Astrocytes
    • Endothelial cells
    • Mouse

    ASJC Scopus subject areas

    • Developmental Biology
    • Molecular Biology

    Cite this

    Sakimoto, S., Kidoya, H., Naito, H., Kamei, M., Sakaguchi, H., Goda, N., ... Takakura, N. (2012). A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice. Development, 139(7), 1327-1335. https://doi.org/10.1242/dev.072330

    A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice. / Sakimoto, Susumu; Kidoya, Hiroyasu; Naito, Hisamichi; Kamei, Motohiro; Sakaguchi, Hirokazu; Goda, Nobuhito; Fukamizu, Akiyoshi; Nishida, Kohji; Takakura, Nobuyuki.

    In: Development, Vol. 139, No. 7, 01.04.2012, p. 1327-1335.

    Research output: Contribution to journalArticle

    Sakimoto, S, Kidoya, H, Naito, H, Kamei, M, Sakaguchi, H, Goda, N, Fukamizu, A, Nishida, K & Takakura, N 2012, 'A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice', Development, vol. 139, no. 7, pp. 1327-1335. https://doi.org/10.1242/dev.072330
    Sakimoto, Susumu ; Kidoya, Hiroyasu ; Naito, Hisamichi ; Kamei, Motohiro ; Sakaguchi, Hirokazu ; Goda, Nobuhito ; Fukamizu, Akiyoshi ; Nishida, Kohji ; Takakura, Nobuyuki. / A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice. In: Development. 2012 ; Vol. 139, No. 7. pp. 1327-1335.
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