Extracellular Signal-Regulated Kinase 1 Alone Is Dispensable for Hyperoxia-Mediated Alveolar and Pulmonary Vascular Simplification in Neonatal Mice

Bronchopulmonary dysplasia (BPD) is a morbid lung disease distinguished by lung alveolar and vascular simplification. Hyperoxia, an important BPD causative factor, increases extracellular signal-regulated kinases (ERK)-1/2 expression, whereas decreased lung endothelial cell expression reduces angiogenesis and potentiates hyperoxia-mediated BPD in mice. However, ERK1's role in experimental BPD is unclear. Thus, we hypothesized that hyperoxia-induced experimental BPD would be more severe in global -knockout () mice than their wild-type ( mice) littermates. We determined the extent of lung development, ERK1/2 expression, inflammation, and oxidative stress in and mice exposed to normoxia (FiO 21%) or hyperoxia (FiO 70%). We also quantified the extent of angiogenesis and hydrogen peroxide (HO) production in hyperoxia-exposed neonatal human pulmonary microvascular endothelial cells (HPMECs) with normal and decreased signaling. Compared with mice, mice displayed increased pulmonary ERK2 activation upon hyperoxia exposure. However, the extent of hyperoxia-induced inflammation, oxidative stress, and interrupted lung development was similar in and mice. knockdown in HPMECs increased ERK2 activation at baseline, but did not affect in vitro angiogenesis and hyperoxia-induced HO production. Thus, we conclude is dispensable for hyperoxia-induced experimental BPD due to compensatory ERK2 activation.