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Updated: Apr 16, 2026
Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice
Rebecca Lim1, Ruth Muljadi2, Eugenia Koulaeva3
11] The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia [2] Department of Obstetrics and Gynecology, Monash University, Victoria, Australia.
Insights
Activin A signaling contributes to bronchopulmonary dysplasia (BPD) development. Inhibiting this pathway with ActRIIB-Fc or follistatin protected neonatal mice from hyperoxia-induced lung injury, suggesting a potential therapeutic target for BPD.
Area of Science:
- Neonatal lung injury research
- TGFβ superfamily signaling pathways
- Pulmonary inflammation and repair
Background:
- Bronchopulmonary dysplasia (BPD) is a major cause of death in premature infants, with no cure.
- Hyperoxia exposure is a key factor in BPD development.
- TGFβ signaling inhibitors show promise in preventing neonatal lung injury.
Purpose of the Study:
- To investigate the role of activin A, a TGFβ superfamily member, in hyperoxia-induced lung injury.
- To assess the therapeutic potential of blocking activin A signaling in a neonatal mouse model of BPD.
Main Methods:
- Newborn mice were exposed to 85% oxygen to induce lung injury mimicking BPD.
- Mice received activin A receptor type IIB-Fc antagonist (ActRIIB-Fc) or follistatin treatments.
- Lung injury, inflammation, and molecular markers were analyzed post-treatment.
Main Results:
- Both ActRIIB-Fc and follistatin treatments prevented growth retardation caused by hyperoxia.
- ActRIIB-Fc reduced lung inflammation and improved lung structure (tissue:airspace ratio, septal crest density).
- Inhibition of activin A signaling decreased Smad3 phosphorylation and matrix metalloproteinase-9 (MMP-9) activity.
Conclusions:
- Activin A signaling plays a significant role in the pathogenesis of hyperoxia-induced lung injury.
- Targeting activin A signaling may offer a novel therapeutic strategy for preventing or treating BPD.
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.
