miR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia

Shaheen Durrani-Kolarik, Caylie A. Pool, Ashley Gray, Kathryn M. Heyob, Mary J. Cismowski, Gloria Pryhuber, L. James Lee, Zhaogang Yang, Trent E. Tipple, Lynette K. Rogers

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 dysregu-lation 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.

Original languageEnglish (US)
Pages (from-to)L339-L349
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume313
Issue number2
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Bronchopulmonary Dysplasia
Hyperoxia
Mothers
Inflammation
Lung
Proteins
Premature Infants
Inbred C3H Mouse
Extracellular Matrix Proteins
Intraperitoneal Injections
Lung Diseases
Chronic Disease
Parturition
Newborn Infant
Oxygen
Morbidity
Therapeutics

Keywords

  • Adeno-associated virus
  • Bronchopulmonary dysplasia
  • Fibrosis
  • Hyperoxia
  • Maternal inflammation
  • MicroRNA

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

miR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia. / Durrani-Kolarik, Shaheen; Pool, Caylie A.; Gray, Ashley; Heyob, Kathryn M.; Cismowski, Mary J.; Pryhuber, Gloria; Lee, L. James; Yang, Zhaogang; Tipple, Trent E.; Rogers, Lynette K.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 313, No. 2, 01.01.2017, p. L339-L349.

Research output: Contribution to journalArticle

Durrani-Kolarik, Shaheen ; Pool, Caylie A. ; Gray, Ashley ; Heyob, Kathryn M. ; Cismowski, Mary J. ; Pryhuber, Gloria ; Lee, L. James ; Yang, Zhaogang ; Tipple, Trent E. ; Rogers, Lynette K. / miR-29b supplementation decreases expression of matrix proteins and improves alveolarization in mice exposed to maternal inflammation and neonatal hyperoxia. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2017 ; Vol. 313, No. 2. pp. L339-L349.
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AU - Pryhuber, Gloria

AU - Lee, L. James

AU - Yang, Zhaogang

AU - Tipple, Trent E.

AU - Rogers, Lynette K.

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