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Neonatology. 2013;104(1):49-55. doi: 10.1159/000350548. Epub 2013 May 24.

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung.

Author information

1
Department of Pediatrics, School of Oncology and Developmental Biology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.

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.

PMID:
23711546
DOI:
10.1159/000350548
[Indexed for MEDLINE]
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