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; Vineet Bhandari

doi:10.1038/s41467-017-01349-y

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

Journal article

Open access

Peer reviewed

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

Nature communications, v 8(1), pp 1173-17

27 Oct 2017

DOI: https://doi.org/10.1038/s41467-017-01349-y

PMID: 29079808

Featured in Collection : UN Sustainable Development Goals @ Drexel

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Abstract

Alveolar Epithelial Cells - metabolism

Angiopoietin-1 - metabolism

Animals

Animals, Newborn

Bronchopulmonary Dysplasia - metabolism

Bronchopulmonary Dysplasia - pathology

Computational Biology

Female

Gene Deletion

Humans

Hyperoxia

Infant, Newborn

Lung - metabolism

Lung - pathology

Male

MicroRNAs - genetics

MicroRNAs - metabolism

Phenotype

Receptor, TIE-2 - metabolism

Signal Transduction

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.

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113 citations in Scopus

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Title: Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs
Creators: Mansoor Syed - Jamia Millia Islamia
Pragnya Das - Drexel University
Aishwarya Pawar - Drexel University
Zubair H Aghai - Thomas Jefferson University
Anu Kaskinen - Helsinki University Hospital
Zhen W Zhuang - Yale University
Namasivayam Ambalavanan - University of Alabama at Birmingham
Gloria Pryhuber - University of Rochester
Sture Andersson - Helsinki University Hospital
Vineet Bhandari - Yale University
Publication Details: Nature communications, v 8(1), pp 1173-17
Publisher: Springer Nature
Grant note: R01 HL063039 / NHLBI NIH HHS UL1 TR001863 / NCATS NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Pediatrics
Web of Science ID: WOS:000413833000017
Scopus ID: 2-s2.0-85032511753
Other Identifier: 991019167685704721

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Collaboration types: Domestic collaboration; International collaboration
Web of Science research areas: Cell Biology

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

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Abstract

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Details

UN Sustainable Development Goals (SDGs)

InCites Highlights

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