MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
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Papangeli-2016-MicroRNA 139-5p.pdf
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Author(s)
Papangeli, Irinna
Kim, Jongmin
Maier, Inna
Park, Saejeong
Lee, Aram
Kang, Yujung
Tanaka, Keiichiro
Ju, Hyekyung
Kojima, Yoko
Red-Horse, Kristy
Date Issued
April 2016
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Papangeli, Irinna, Jongmin Kim, Inna Maier, Saejeong Park, Aram Lee, Yujung Kang, Keiichiro Tanaka, et al. “MicroRNA 139-5p Coordinates APLNR-CXCR4 Crosstalk During Vascular Maturation.” Nat Comms 7 (April 12, 2016): 11268. © 2017 Macmillan Publishers Limited
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Final published version
Abstract
G protein-coupled receptor (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be important in vascular development. How this ligand–receptor pair regulates the downstream signalling cascades in this context remains poorly understood. Here, we show that mice with Apln, Aplnr or endothelial-specific Aplnr deletion develop profound retinal vascular defects, which are at least in part due to dysregulated increase in endothelial CXCR4 expression. Endothelial CXCR4 is negatively regulated by miR-139-5p, whose transcription is in turn induced by laminar flow and APLN/APLNR signalling. Inhibition of miR-139-5p in vivo partially phenocopies the retinal vascular defects of APLN/APLNR deficiency. Pharmacological inhibition of CXCR4 signalling or augmentation of the miR-139-5p-CXCR4 axis can ameliorate the vascular phenotype of APLN/APLNR deficient state. Overall, we identify an important microRNA-mediated GPCR crosstalk, which plays a key role in vascular development.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1038/ncomms11268
