Abstract
Background:
Bronchopulmonary dysplasia (BPD) is one of the leading causes of morbidity and mortality in babies born prematurely, yet there is no curative treatment. In recent years, a number of inhibitors against TGFβ signaling have been tested for their potential to prevent neonatal injury associated with hyperoxia, which is a contributing factor of BPD. In this study, we assessed the contribution of activin A—a member of the TGFβ superfamily—to the development of hyperoxia-induced lung injury in neonatal mice.
Methods:
We placed newborn C57Bl6 mouse pups in continuous hyperoxia (85% O2) to mimic many aspects of BPD including alveolar simplification and pulmonary inflammation. The pups were administered activin A receptor type IIB-Fc antagonist (ActRIIB-Fc) at 5 mg/kg or follistatin at 0.1 mg/kg on postnatal days 4, 7, 10, and 13.
Results:
Treatment with ActRIIB-Fc and follistatin protected against hyperoxia-induced growth retardation. ActRIIB-Fc also reduced pulmonary leukocyte infiltration, normalized tissue: airspace ratio and increased septal crest density. These findings were associated with reduced phosphorylation of Smad3 and decreased matrix metalloproteinase (MMP)-9 activity.
Conclusion:
This study suggests that activin A signaling may contribute to the pathology of bronchopulmonary dysplasia.
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Lim, R., Muljadi, R., Koulaeva, E. et al. Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice. Pediatr Res 77, 749–756 (2015). https://doi.org/10.1038/pr.2015.46
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DOI: https://doi.org/10.1038/pr.2015.46
