Journal Article

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

Pawar, Aishwarya, Aghai, Zubair H., Kaskinen, Anu, Das, Pragnya, Ambalavanan, Namasivayam, Bhandari, Vineet, Zhuang, Zhen W., Pryhuber, Gloria, Andersson, Sture, Syed, Mansoor

2017

Overview

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. Hyperoxia contributes to lung injury in bronchopulmonary dysplasia. The authors show that hyperoxia increases miR-34a expression in human neonates and in mouse models, and that pathology is ameliorated by miR-34a inhibition or by administration of its target angiopoietin-1

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/337/384/331 / 692/1807/244 / 692/699/1785 / Alveolar Epithelial Cells - metabolism / Alveoli / Angiopoietin / Angiopoietin-1 - metabolism / Animal models / Animals / Animals, Newborn / Bronchopulmonary Dysplasia - metabolism / Bronchopulmonary Dysplasia - pathology / Chemical compounds / Clonal deletion / Computational Biology / Dysplasia / Epithelial cells / Female / Gene Deletion / Humanities and Social Sciences / Humans / Hyperoxia / Hypertension / Infant, Newborn / Injury prevention / Lung - metabolism / Lung - pathology / Lungs / Male / MicroRNAs - genetics / MicroRNAs - metabolism / multidisciplinary / Neonates / Pathogenesis / Pharmacology / Phenotype / Pulmonary hypertension / Receptor, TIE-2 - metabolism / Respiratory distress syndrome / Ribonucleic acid / RNA / Rodents / Science / Science (multidisciplinary) / Signal Transduction