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

Author

Listed:
  • Irinna Papangeli

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Jongmin Kim

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine
    Sookmyung Women’s University)

  • Inna Maier

    (Max Planck Institute for Molecular Biomedicine)

  • Saejeong Park

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Aram Lee

    (Sookmyung Women’s University)

  • Yujung Kang

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Keiichiro Tanaka

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Omar F. Khan

    (David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Hyekyung Ju

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Yoko Kojima

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

  • Kristy Red-Horse

    (Stanford University)

  • Daniel G. Anderson

    (David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology)

  • Arndt F. Siekmann

    (Max Planck Institute for Molecular Biomedicine)

  • Hyung J. Chun

    (Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Yale University School of Medicine)

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.

Suggested Citation

  • Irinna Papangeli & Jongmin Kim & Inna Maier & Saejeong Park & Aram Lee & Yujung Kang & Keiichiro Tanaka & Omar F. Khan & Hyekyung Ju & Yoko Kojima & Kristy Red-Horse & Daniel G. Anderson & Arndt F. Si, 2016. "MicroRNA 139-5p coordinates APLNR-CXCR4 crosstalk during vascular maturation," Nature Communications, Nature, vol. 7(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11268
    DOI: 10.1038/ncomms11268
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    Cited by:

    1. Massimiliano Bissa & Sohyoung Kim & Veronica Galli & Slim Fourati & Sarkis Sarkis & Anush Arakelyan & Isabela Silva Castro & Mohammad Arif Rahman & Saori Fujiwara & Monica Vaccari & Jeffrey A. Tomalka, 2023. "HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Hongryeol Park & Jian Song & Hyun-Woo Jeong & Max L. B. Grönloh & Bong Ihn Koh & Esther Bovay & Kee-Pyo Kim & Luisa Klotz & Patricia A. Thistlethwaite & Jaap D. Buul & Lydia Sorokin & Ralf H. Adams, 2024. "Apelin modulates inflammation and leukocyte recruitment in experimental autoimmune encephalomyelitis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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