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

Development
Susumu SakimotoNobuyuki Takakura

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.

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Citations

Jun 30, 2012·Journal of Biochemistry·Hiroyasu Kidoya, Nobuyuki Takakura
Mar 23, 2013·PloS One·Susumu SakimotoNobuyuki Takakura
Nov 8, 2015·Biochemical and Biophysical Research Communications·Qi-Feng LiuBao-Ze Qu
Apr 14, 2016·Nature Communications·Irinna PapangeliHyung J Chun
Aug 27, 2013·Biochemical and Biophysical Research Communications·Qi-Feng LiuGui-Zhou Tao
Dec 30, 2016·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Akane MoritaTsutomu Nakahara
Jan 20, 2018·Journal of Cellular Physiology·Jin XuLanfang Li
Jul 15, 2021·Developmental Biology·Caitlin E Paisley, Jeremy N Kay
Aug 8, 2021·Cancers·Roland E Kälin, Rainer Glass
Jul 24, 2021·Experimental Neurology·Akhil SharmaAnna Moszczynska

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