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. 2019 Nov;86(5):579-588.
doi: 10.1038/s41390-019-0524-3. Epub 2019 Aug 8.

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

Mohammad Afaque Alam  1   2 , Suhita Gayen Nee Betal  3 , Zubair H Aghai  3 , Vineet Bhandari  4
Affiliations

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

Mohammad Afaque Alam et al. Pediatr Res. 2019 Nov.

Abstract

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.

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