| First Author | Papangeli I | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 11268 | PubMed ID | 27068353 |
| Mgi Jnum | J:236895 | Mgi Id | MGI:5810051 |
| Doi | 10.1038/ncomms11268 | Citation | Papangeli I, et al. (2016) MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation. Nat Commun 7:11268 |
| abstractText | 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. |
