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Vol. 104, No. 1, 2013
Issue release date: July 2013
Section title: Original Paper
Neonatology 2013;104:49-55
(DOI:10.1159/000350548)

Repeated Intrauterine Exposures to Inflammatory Stimuli Attenuated Transforming Growth Factor-β Signaling in the Ovine Fetal Lung

Collins J.J.P. · Kallapur S.G. · Knox C.L. · Kemp M.W. · Kuypers E. · Zimmermann L.J.I. · Newnham J.P. · Jobe A.H. · Kramer B.W.
aDepartment of Pediatrics, School of Oncology and Developmental Biology, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands; bCincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA; cSchool of Women's and Infant's Health, The University of Western Australia, Perth, W.A., and dInstitute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology, Brisbane, Qld., Australia

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 10/23/2012 11:30:41 AM
Accepted: 3/1/2013
Published online: 5/24/2013

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO

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.


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 10/23/2012 11:30:41 AM
Accepted: 3/1/2013
Published online: 5/24/2013

Number of Print Pages: 7
Number of Figures: 1
Number of Tables: 3

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


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