Document Type
Article
Publication Date
10-27-2017
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.
Recommended Citation
Syed, Mansoor; Das, Pragnya; Pawar, Aishwarya; Aghai, Zubair H.; Kaskinen, Anu; Zhuang, Zhen W.; Ambalavanan, Namasivayam; Pryhuber, Gloria; Andersson, Sture; and Bhandari, Vineet, "Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs." (2017). Department of Pediatrics Faculty Papers. Paper 73.
https://jdc.jefferson.edu/pedsfp/73
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
29079808
Comments
This article has been peer reviewed. It is the author’s final published version in Nature Communications
Volume 8, Issue 1, October 2017, Article number 1173.
The published version is available at DOI: 10.1038/s41467-017-01349-y. Copyright © Syed et al.