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Nadph oxidase and epithelial sodium channels regulate neonatal mouse lung development

1 Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30322, USA
2 Department of Internal Medicine, University of Utah, Salt Lake City, UT 84132, USA

Background: Epithelial sodium channels (ENaC) play critically important roles in lung fluid clearance at birth. We have previously shown that Nadph oxidase (NOX)-derived reactive oxygen species signaling activates ENaC and promotes alveolar fluid clearance. In this study, we examined a new physiological role for NOX-mediated ENaC activity in mouse lung development. Methods: NOX isoform and ENaC subunit mRNA levels were evaluated in preterm and neonatal C57Bl6 mouse lung using real-time PCR analysis. Newborn mice were intra-nasally treated with 1 mM amiloride, 100 mM NSC 23766, or 300 mM apocynin during postnatal days 1–15 to study development. Lung development was assessed using hematoxylin and eosin (H&E) staining, coupled with radial alveolar counts (RAC) and mean linear intercept (MLI) measurements. Results: ENaC subunits and NOX1-4 mRNA were detected in mouse lung during late gestation, birth, and postnatally. Inhibition of Rac-1-mediated-NOX signaling indicates functional (Rac-dependent) NOX1-3 isoforms in newborn lung, determined by dihydroethidium (DHE) detection of reactive oxygen species production in postnatal (PN) day 7 mouse lung. Amiloride inhibition of ENaC activity, NSC 23766 inhibition of Rac1, and apocynin inhibition of pan NOX activity attenuated normal alveolar development in mouse lung. Conclusion: NOX and ENaC play important roles in mouse lung development.
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Keywords epithelial sodium channels; Nadph oxidase; oxygen therapy; preterm birth

Citation: David Trac, My N. Helms. Nadph oxidase and epithelial sodium channels regulate neonatal mouse lung development. AIMS Molecular Science, 2017, 4(1): 28-40. doi: 10.3934/molsci.2017.1.28


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