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*

*この研究の対応する著者

研究成果: Article査読

43 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1327-1335
ページ数9
ジャーナルDevelopment
139
7
DOI
出版ステータスPublished - 2012 4月 1

ASJC Scopus subject areas

  • 分子生物学
  • 発生生物学

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