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- Title
Repeated Intrauterine Exposures to Inflammatory Stimuli Attenuated Transforming Growth Factor-β Signaling in the Ovine Fetal Lung.
- Authors
Collins, Jennifer J.P.; Kallapur, Suhas G.; Knox, Christine L.; Kemp, Matthew W.; Kuypers, Elke; Zimmermann, Luc J.I.; Newnham, John P.; Jobe, alan H.; Kramer, Boris W.
- Abstract
Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition. Copyright © 2013 S. Karger AG, Basel
- Subjects
BRONCHOPULMONARY dysplasia; PREMATURE infants; LIPOPOLYSACCHARIDES; AMNIOTIC liquid; IMMUNE response
- Publication
Neonatology (16617800), 2013, Vol 104, Issue 1, p49
- ISSN
1661-7800
- Publication type
Article
- DOI
10.1159/000350548