MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
Citations Over TimeTop 10% of 2016 papers
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.
Related Papers
- → Apelin, diabetes, and obesity(2011)289 cited
- → Angiotensin-Converting Enzyme 2 Metabolizes and Partially Inactivates Pyr-Apelin-13 and Apelin-17(2016)194 cited
- → Targeting the apelin pathway as a novel therapeutic approach for cardiovascular diseases(2016)104 cited
- → Cardiovascular effects of a PEGylated apelin(2012)50 cited
- → The induction of a multiple wing hair phenocopy by heat shock in mutant heterozygotes(1987)31 cited