Hyperoxia causes miR199a-5p-mediated injury in the developing lung

Background Hyperoxia-induced acute lung injury (HALI) is characterized by increased permeability and infiltration of inflammatory cells, impairment of alveolar development, and compromised lung function. Recent evidence has determined that microRNAs (miRs) are implicated in hyperoxia-induced lung in...

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Published in:Pediatric research 2019-11, Vol.86 (5), p.579-588
Main Authors: Alam, Mohammad Afaque, Betal, Suhita Gayen nee, Aghai, Zubair H., Bhandari, Vineet
Format: Article
Language:English
Subjects:
Animals
Basic Science Article
Bronchopulmonary Dysplasia - etiology
Bronchopulmonary Dysplasia - genetics
Capillary Permeability
Developmental biology
Female
Gene Expression Profiling
Humans
Hyperoxia
Hyperoxia - complications
Infant, Newborn
Lung - blood supply
Lung - growth & development
Lungs
Male
Medicine
Medicine & Public Health
Mice
Mice, Inbred C57BL
MicroRNAs
MicroRNAs - genetics
MicroRNAs - physiology
Pediatric Surgery
Pediatrics
RAW 264.7 Cells
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Summary:Background Hyperoxia-induced acute lung injury (HALI) is characterized by increased permeability and infiltration of inflammatory cells, impairment of alveolar development, and compromised lung function. Recent evidence has determined that microRNAs (miRs) are implicated in hyperoxia-induced lung injury, including bronchopulmonary dysplasia (BPD). However, the expression profile and functional role of miR199a-5p in developing lungs have not been reported. Methods The present study was undertaken to explore the role of miR199a-5p in developing mice lungs and human neonates. We exposed neonatal mice for 7 days, mouse lung epithelial cells (MLE12), mouse lung endothelial cells (MLECs), and macrophages (RAW246.7), to hyperoxia at different time points. Results Our results demonstrated enhanced miR199a-5p expression in hyperoxia-exposed mice lungs and cells, as well as in tracheal aspirates of infants developing BPD, with significant reduction in the expression of its target, caveolin-1. Next, we observed that miR199a-5p-mimic worsens HALI as evidenced by increased inflammatory cells, cytokines, and lung vascular markers. Conversely, miR199a-5p-inhibitor treatment attenuated HALI. Conclusion Thus, our findings suggest that miR199a-5p is a potential target for attenuating HALI pathophysiology in the developing lung. Moreover, miR199a-5p-inhibitor could be part of a novel therapeutic strategy for improving BPD in preterm neonates.
ISSN:0031-3998
1530-0447
DOI:10.1038/s41390-019-0524-3