MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturationopen access
- Authors
- Papangeli, Irinna; Kim, Jongmin; Maier, Inna; Park, Saejeong; Lee, Aram; Kang, Yujung; Tanaka, Keiichiro; Khan, Omar F.; Ju, Hyekyung; Kojima, Yoko; Red-Horse, Kristy; Anderson, Daniel G.; Siekmann, Arndt F.; Chun, Hyung J.
- Issue Date
- Apr-2016
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE COMMUNICATIONS, v.7
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 7
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9845
- DOI
- 10.1038/ncomms11268
- ISSN
- 2041-1723
- 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.
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