RGD Reference Report - Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice. - Rat Genome Database

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

Authors: Lim, Rebecca  Muljadi, Ruth  Koulaeva, Eugenia  Vosdoganes, Patricia  Chan, Siow Teng  Acharya, Rutu  Gurusinghe, Seshini  Ritvos, Olli  Pasternack, Arja  Wallace, Euan M 
Citation: Lim R, etal., Pediatr Res. 2015 Jun;77(6):749-56. doi: 10.1038/pr.2015.46. Epub 2015 Mar 11.
RGD ID: 13204816
Pubmed: PMID:25760549   (View Abstract at PubMed)
DOI: DOI:10.1038/pr.2015.46   (Journal Full-text)


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 TGFß 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 TGFß 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MMP9HumanHyperoxic Lung Injury treatmentISOMmp9 (Mus musculus) RGD 
Mmp9RatHyperoxic Lung Injury treatmentISOMmp9 (Mus musculus) RGD 
Mmp9MouseHyperoxic Lung Injury treatmentIEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information