title: Activin A contributes to the development of hyperoxia-induced lung injury in neonatal mice.
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.
  
  
  CONCLUSIONS
  This study suggests that activin A signaling may contribute to the pathology of bronchopulmonary dysplasia.
authors.affiliation: 1] The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia [2] Department of Obstetrics and Gynecology, Monash University, Victoria, Australia.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Lim
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Muljadi
authors.affiliation: Department of Obstetrics and Gynecology, Monash University, Victoria, Australia.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Koulaeva
authors.affiliation: Department of Obstetrics and Gynecology, Monash University, Victoria, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Vosdoganes
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia.
authors.forename: Siow Teng
authors.initials: ST
authors.lastname: Chan
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia.
authors.forename: Rutu
authors.initials: R
authors.lastname: Acharya
authors.affiliation: The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia.
authors.forename: Seshini
authors.initials: S
authors.lastname: Gurusinghe
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Olli
authors.initials: O
authors.lastname: Ritvos
authors.affiliation: Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Pasternack
authors.affiliation: 1] The Ritchie Centre, MIMR-PHI Institute of Medical Research, Victoria, Australia [2] Department of Obstetrics and Gynecology, Monash University, Victoria, Australia.
authors.forename: Euan M
authors.initials: EM
authors.lastname: Wallace
mesh_terms: D030301:Activin Receptors, Type II / Q000037:antagonists & inhibitors*; D028341:Activins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D038681:Follistatin / Q000494:pharmacology; D006130:Growth Disorders / Q000517:prevention & control; D018496:Hyperoxia / Q000473:pathology*; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D051900:Smad3 Protein / Q000378:metabolism
chemical_list: D038681:Follistatin; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; C422405:activin A; D028341:Activins; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse