Altered canonical Wingless-Int signaling in the ovine fetal lung after exposure to intra-amniotic lipopolysaccharide and antenatal betamethasone

Elke Kuypers, Monique G M Willems, Jennifer J P Collins, Tim G A M Wolfs, Ilias Nitsos, Jane Pillow, Graeme Polglase, Matthew W Kemp, John P Newnham, Tammo Delhaas, Alan H Jobe, Suhas G Kallapur, Boris W Kramer

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BackgroundAntenatal inflammation and maternal corticosteroids induce fetal lung maturation but interfere with late lung development. Canonical Wingless-Int (Wnt) signaling directs lung development and repair. We showed that intra-amniotic lipopolysaccharide (LPS) exposure disrupted developmental signaling pathways in the preterm lamb lungs. Therefore, we hypothesized that pulmonary Wnt signaling was altered by exposure to intra-amniotic LPS and/or antenatal corticosteroids.MethodsOvine fetuses were exposed to intra-amniotic LPS, maternal intra-muscular betamethasone, a control saline injection or a combination thereof at 107 and/or 114d gestational age (GA) (term=150d GA) before delivery at 121d GA.ResultsIntra-amniotic LPS exposure decreased the lung expression of lymphoid enhancer-binding factor 1 (LEF1), a major Wnt pathway effector. WNT1, WNT4 and downstream messenger beta-catenin decreased after LPS exposure. WNT7b mRNA increased 4-fold 14d post LPS exposure. Betamethasone treatment 7d before LPS exposure prevented the reduction in LEF1 expression whereas betamethasone administration after LPS normalized the LPS-induced increase in Wnt7b mRNA.ConclusionIntra-amniotic LPS exposure decreased canonical Wnt signaling in the developing lung. Antenatal corticosteroids before or after intra-amniotic inflammation had different effects on pulmonary Wnt signaling. This study provides new insights into possible mechanisms by which prenatal inflammation affects lung development and how corticosteroid can be beneficial in this setting.Pediatric Research (2013); doi:10.1038/pr.2013.226.
Original languageEnglish
Pages (from-to)281 - 287
Number of pages7
JournalPediatric Research
Issue number2
Publication statusPublished - 2014

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