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

First Author  Sakimoto S Year  2012
Journal  Development Volume  139
Issue  7 Pages  1327-35
PubMed ID  22357924 Mgi Jnum  J:182743
Mgi Id  MGI:5316533 Doi  10.1242/dev.072330
Citation  Sakimoto S, et al. (2012) A role for endothelial cells in promoting the maturation of astrocytes through the apelin/APJ system in mice. Development 139(7):1327-35
abstractText  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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