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

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Syed , M , Das , P , Pawar , A , Aghai , Z H , Kaskinen , A , Zhuang , Z W , Ambalavanan , N , Pryhuber , G , Andersson , S & Bhandari , V 2017 , ' Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs ' , Nature Communications , vol. 8 , 1173 . https://doi.org/10.1038/s41467-017-01349-y

Title: Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs
Author: Syed, Mansoor; Das, Pragnya; Pawar, Aishwarya; Aghai, Zubair H.; Kaskinen, Anu; Zhuang, Zhen W.; Ambalavanan, Namasivayam; Pryhuber, Gloria; Andersson, Sture; Bhandari, Vineet
Contributor: University of Helsinki, Clinicum
University of Helsinki, HUS Children and Adolescents
Date: 2017-10-27
Language: eng
Number of pages: 17
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/228661
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.
Subject: MESENCHYMAL STEM-CELLS
BRONCHOPULMONARY-DYSPLASIA
EPITHELIAL-CELLS
MIR-200 FAMILY
MOUSE LUNG
EXPRESSION
APOPTOSIS
PROTECTS
PATHWAY
MICRORNAS
3123 Gynaecology and paediatrics
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