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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents



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ID: 732113.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation
Authors:Papangeli, I.; Kim, J.; Maier, I.; Park, S.; Lee, A.; Kang, Y.; Tanaka, K.; Khan, O. F.; Ju, H.; Kojima, Y.; Red-Horse, K.; Anderson, D. G.; Siekmann, A. F.; Chun, H. J.
Date of Publication (YYYY-MM-DD):2016-04-12
Title of Journal:Nat Commun
Volume:7
Start Page:11268
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Adipokines/metabolism; Animals; Atorvastatin Calcium/pharmacology; Down-Regulation; Endothelial Cells/metabolism; Hemorheology; Intercellular Signaling Peptides and Proteins/metabolism; Mice, Inbred C57BL; MicroRNAs/genetics/*metabolism; Phenotype; *Receptor Cross-Talk; Receptors, CXCR4/*metabolism; Receptors, G-Protein-Coupled/*metabolism; Retinal Vessels/*growth & development/*metabolism
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Korea. Max Planck Institute for Molecular Biomedicine, Roentgenstr. 20, 48149 Muenster, Germany. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA. Department of Biological Sciences, Stanford University, Stanford, California 94305, USA.
Identifiers:ISSN:2041-1723 (Electronic) 2041-1723 (Linking) %R 10.1... [ID No:1]
URL:https://www.ncbi.nlm.nih.gov/pubmed/27068353 [ID No:2]
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