miR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia.
Am J Physiol Lung Cell Mol Physiol
; 313(2): L339-L349, 2017 08 01.
Article
em En
| MEDLINE
| ID: mdl-28473324
ABSTRACT
Even with advances in the care of preterm infants, chronic lung disease or bronchopulmonary dysplasia (BPD) continues to be a significant pulmonary complication. Among those diagnosed with BPD, a subset of infants develop severe BPD with disproportionate pulmonary morbidities. In addition to decreased alveolarization, these infants develop obstructive and/or restrictive lung function due to increases in or dysregulation of extracellular matrix proteins. Analyses of plasma obtained from preterm infants during the first week of life indicate that circulating miR-29b is suppressed in infants that subsequently develop BPD and that decreased circulating miR-29b is inversely correlated with BPD severity. Our mouse model mimics the pathophysiology observed in infants with severe BPD, and we have previously reported decreased pulmonary miR-29b expression in this model. The current studies tested the hypothesis that adeno-associated 9 (AAV9)-mediated restoration of miR-29b in the developing lung will improve lung alveolarization and minimize the deleterious changes in matrix deposition. Pregnant C3H/HeN mice received an intraperitoneal LPS injection on embryonic day 16 and newborn pups were exposed to 85% oxygen from birth to 14 days of life. On postnatal day 3, AAV9-miR-29b or AAV9-control was administered intranasally. Mouse lung tissues were then analyzed for changes in miR-29 expression, alveolarization, and matrix protein levels and localization. Although only modest improvements in alveolarization were detected in the AAV9-miR29b-treated mice at postnatal day 28, treatment completely attenuated defects in matrix protein expression and localization. Our data suggest that miR-29b restoration may be one component of a novel therapeutic strategy to treat or prevent severe BPD in prematurely born infants.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Matriz Extracelular
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Hiperóxia
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MicroRNAs
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Inflamação
Limite:
Animals
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Humans
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Newborn
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article