PT  - JOURNAL ARTICLE
AU  - Thomas M. Raffay
AU  - Andrew M. Dylag
AU  - Juliann M. Di Fiore
AU  - Laura A. Smith
AU  - Helly J. Einisman
AU  - Yuejin Li
AU  - Mitchell M. Lakner
AU  - Ahmad M. Khalil
AU  - Peter M. MacFarlane
AU  - Richard J. Martin
AU  - Benjamin Gaston
TI  - S-Nitrosoglutathione Attenuates Airway Hyperresponsiveness in Murine Bronchopulmonary Dysplasia
AID  - 10.1124/mol.116.104125
DP  - 2016 Oct 01
TA  - Molecular Pharmacology
PG  - 418--426
VI  - 90
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/90/4/418.short
4100  - http://molpharm.aspetjournals.org/content/90/4/418.full
SO  - Mol Pharmacol2016 Oct 01; 90
AB  - Bronchopulmonary dysplasia (BPD) is characterized by lifelong obstructive lung disease and profound, refractory bronchospasm. It is observed among survivors of premature birth who have been treated with prolonged supplemental oxygen. Therapeutic options are limited. Using a neonatal mouse model of BPD, we show that hyperoxia increases activity and expression of a mediator of endogenous bronchoconstriction, S-nitrosoglutathione (GSNO) reductase. MicroRNA-342-3p, predicted in silico and shown in this study in vitro to suppress expression of GSNO reductase, was decreased in hyperoxia-exposed pups. Both pretreatment with aerosolized GSNO and inhibition of GSNO reductase attenuated airway hyperresponsiveness in vivo among juvenile and adult mice exposed to neonatal hyperoxia. Our data suggest that neonatal hyperoxia exposure causes detrimental effects on airway hyperreactivity through microRNA-342-3p–mediated upregulation of GSNO reductase expression. Furthermore, our data demonstrate that this adverse effect can be overcome by supplementing its substrate, GSNO, or by inhibiting the enzyme itself. Rates of BPD have not improved over the past two decades; nor have new therapies been developed. GSNO-based therapies are a novel treatment of the respiratory problems that patients with BPD experience.