| First Author | McKenna S | Year | 2014 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 306 |
| Issue | 12 | Pages | L1078-89 |
| PubMed ID | 24748603 | Mgi Jnum | J:221745 |
| Mgi Id | MGI:5641438 | Doi | 10.1152/ajplung.00001.2014 |
| Citation | McKenna S, et al. (2014) Sustained hyperoxia-induced NF-kappaB activation improves survival and preserves lung development in neonatal mice. Am J Physiol Lung Cell Mol Physiol 306(12):L1078-89 |
| abstractText | Oxygen toxicity contributes to the pathogenesis of bronchopulmonary dysplasia (BPD). Neonatal mice exposed to hyperoxia develop a simplified lung structure that resembles BPD. Sustained activation of the transcription factor NF-kappaB and increased expression of protective target genes attenuate hyperoxia-induced mortality in adults. However, the effect of enhancing hyperoxia-induced NF-kappaB activity on lung injury and development in neonatal animals is unknown. We performed this study to determine whether sustained NF-kappaB activation, mediated through IkappaBbeta overexpression, preserves lung development in neonatal animals exposed to hyperoxia. Newborn wild-type (WT) and IkappaBbeta-overexpressing (AKBI) mice were exposed to hyperoxia (>95%) or room air from day of life (DOL) 0-14, after which all animals were kept in room air. Survival curves were generated through DOL 14. Lung development was assessed using radial alveolar count (RAC) and mean linear intercept (MLI) at DOL 3 and 28 and pulmonary vessel density at DOL 28. Lung tissue was collected, and NF-kappaB activity was assessed using Western blot for IkappaB degradation and NF-kappaB nuclear translocation. WT mice demonstrated 80% mortality through 14 days of exposure. In contrast, AKBI mice demonstrated 60% survival. Decreased RAC, increased MLI, and pulmonary vessel density caused by hyperoxia in WT mice were significantly attenuated in AKBI mice. These findings were associated with early and sustained NF-kappaB activation and expression of cytoprotective target genes, including vascular endothelial growth factor receptor 2. We conclude that sustained hyperoxia-induced NF-kappaB activation improves neonatal survival and preserves lung development. Potentiating early NF-kappaB activity after hyperoxic exposure may represent a therapeutic intervention to prevent BPD. |
