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Nat Commun. 2016 Apr 12;7:11268. doi: 10.1038/ncomms11268.

MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation.

Author information

1
Department of Internal Medicine, Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine, 300 George Street, 7th Floor, New Haven, Connecticut 06511, USA.
2
Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Korea.
3
Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany.
4
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA.
5
Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.

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.

PMID:
27068353
PMCID:
PMC4832062
DOI:
10.1038/ncomms11268
[Indexed for MEDLINE]
Free PMC Article

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