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Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs

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  • Mansoor Syed

    (Division of Perinatal Medicine, Department of Pediatrics Yale University School of Medicine
    Section of Neonatology, Department of Pediatrics Drexel University College of Medicine
    Jamia Millia Islamia)

  • Pragnya Das

    (Section of Neonatology, Department of Pediatrics Drexel University College of Medicine)

  • Aishwarya Pawar

    (Section of Neonatology, Department of Pediatrics Drexel University College of Medicine)

  • Zubair H. Aghai

    (Section of Neonatology, Department of Pediatrics Thomas Jefferson University)

  • Anu Kaskinen

    (Children’s Hospital, University of Helsinki and Helsinki University Hospital Helsinki)

  • Zhen W. Zhuang

    (Section of Cardiovascular Medicine, Department of Medicine Yale University School of Medicine)

  • Namasivayam Ambalavanan

    (Division of Neonatology, Department of Pediatrics University of Alabama at Birmingham)

  • Gloria Pryhuber

    (University of Rochester School of Medicine and Dentistry)

  • Sture Andersson

    (Children’s Hospital, University of Helsinki and Helsinki University Hospital Helsinki)

  • Vineet Bhandari

    (Division of Perinatal Medicine, Department of Pediatrics Yale University School of Medicine
    Section of Neonatology, Department of Pediatrics Drexel University College of Medicine)

Abstract

Hyperoxia-induced acute lung injury (HALI) is a key contributor to the pathogenesis of bronchopulmonary dysplasia (BPD) in neonates, for which no specific preventive or therapeutic agent is available. Here we show that lung micro-RNA (miR)-34a levels are significantly increased in lungs of neonatal mice exposed to hyperoxia. Deletion or inhibition of miR-34a improves the pulmonary phenotype and BPD-associated pulmonary arterial hypertension (PAH) in BPD mouse models, which, conversely, is worsened by miR-34a overexpression. Administration of angiopoietin-1, which is one of the downstream targets of miR34a, is able to ameliorate the BPD pulmonary and PAH phenotypes. Using three independent cohorts of human samples, we show that miR-34a expression is increased in type 2 alveolar epithelial cells in neonates with respiratory distress syndrome and BPD. Our data suggest that pharmacologic miR-34a inhibition may be a therapeutic option to prevent or ameliorate HALI/BPD in neonates.

Suggested Citation

  • Mansoor Syed & Pragnya Das & Aishwarya Pawar & Zubair H. Aghai & Anu Kaskinen & Zhen W. Zhuang & Namasivayam Ambalavanan & Gloria Pryhuber & Sture Andersson & Vineet Bhandari, 2017. "Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01349-y
    DOI: 10.1038/s41467-017-01349-y
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