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.
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.
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