Abstract
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infants with lifelong pulmonary and neurodevelopmental consequences. The pathogenesis of BPD is contributed by genetic and environmental factors; among the latter, a critical contributor is exposure of the developing lung to hyperoxia. We have recently reported (Nat Comm 8:1173) that hyperoxia exposure in our in vitro and in vivo modeling systems of hyperoxia-induced lung injury (HALI) and BPD leads to an upregulation of the microRNA (miR) 34a. Utilizing genetic loss- and gain- of function strategies, we show that miR34a inhibition ameliorates the pulmonary phenotype of BPD (including BPD-associated pulmonary hypertension), at least in part, via one of the downstream targets of miR34a, namely Angiopoietin1/Tie 2 signaling. In addition, we demonstrate translational clinical significance of our findings by showing increased miR34a and decreased Ang1 expression in 3 independent cohorts of human lung samples.