Neonatology · 2013
Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.
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.
Предметные рубрики MeSH
AmnionAnimalsChorioamnionitisDisease Models, AnimalElastinFemaleGestational AgeInflammationLipopolysaccharidesLungPhosphorylationPregnancyPregnancy ComplicationsReceptors, Transforming Growth Factor betaSheepSignal TransductionSmad2 ProteinTransforming Growth Factor betaTransforming Growth Factor beta1Transforming Growth Factor beta2Transforming Growth Factor beta3Ureaplasma