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

Mansoor Syed, Pragnya Das, Aishwarya Pawar, Zubair H. Aghai, Anu Kaskinen, Zhen W. Zhuang, Namasivayam Ambalavanan, Gloria Pryhuber, Sture Andersson and Vineet Bhandari ()
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Mansoor Syed: Division of Perinatal Medicine, Department of Pediatrics Yale University School of Medicine
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

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01349-y

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