Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

Rebecca Seok Wai Lim, Ruth Cecilia Magdalene Muljadi, Eugenia Koulaeva, Patricia Vosdoganes, Siow Teng Chan, Rutu Acharya, Seshini Gurusinghe, Olli Ritvos, Arja Pasternack, Euan Morrison Wallace

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

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 TGF? 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 TGF? 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.
Original languageEnglish
Pages (from-to)749 - 756
Number of pages8
JournalPediatric Research
Volume77
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

Lim, Rebecca Seok Wai ; Muljadi, Ruth Cecilia Magdalene ; Koulaeva, Eugenia ; Vosdoganes, Patricia ; Chan, Siow Teng ; Acharya, Rutu ; Gurusinghe, Seshini ; Ritvos, Olli ; Pasternack, Arja ; Wallace, Euan Morrison. / Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice. In: Pediatric Research. 2015 ; Vol. 77, No. 6. pp. 749 - 756.
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abstract = "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 TGF? 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 TGF? 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.",
author = "Lim, {Rebecca Seok Wai} and Muljadi, {Ruth Cecilia Magdalene} and Eugenia Koulaeva and Patricia Vosdoganes and Chan, {Siow Teng} and Rutu Acharya and Seshini Gurusinghe and Olli Ritvos and Arja Pasternack and Wallace, {Euan Morrison}",
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Lim, RSW, Muljadi, RCM, Koulaeva, E, Vosdoganes, P, Chan, ST, Acharya, R, Gurusinghe, S, Ritvos, O, Pasternack, A & Wallace, EM 2015, 'Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice', Pediatric Research, vol. 77, no. 6, pp. 749 - 756. https://doi.org/10.1038/pr.2015.46

Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice. / Lim, Rebecca Seok Wai; Muljadi, Ruth Cecilia Magdalene; Koulaeva, Eugenia; Vosdoganes, Patricia; Chan, Siow Teng; Acharya, Rutu; Gurusinghe, Seshini; Ritvos, Olli; Pasternack, Arja; Wallace, Euan Morrison.

In: Pediatric Research, Vol. 77, No. 6, 2015, p. 749 - 756.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice

AU - Lim, Rebecca Seok Wai

AU - Muljadi, Ruth Cecilia Magdalene

AU - Koulaeva, Eugenia

AU - Vosdoganes, Patricia

AU - Chan, Siow Teng

AU - Acharya, Rutu

AU - Gurusinghe, Seshini

AU - Ritvos, Olli

AU - Pasternack, Arja

AU - Wallace, Euan Morrison

PY - 2015

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N2 - 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 TGF? 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 TGF? 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.

AB - 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 TGF? 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 TGF? 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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