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 journalArticlepeer-review

32 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

Keywords

  • Apelin
  • Astrocytes
  • Endothelial cells
  • Mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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