Alcazar, Miguel Angel Alejandre, Dinger, Katharina, Rother, Eva, Oestreicher, Iris, Vohlen, Christina, Plank, Christian and Doetsch, Joerg (2014). Prevention of Early Postnatal Hyperalimentation Protects against Activation of Transforming Growth Factor-beta/Bone Morphogenetic Protein and Interleukin-6 Signaling in Rat Lungs after Intrauterine Growth Restriction. J. Nutr., 144 (12). S. 1943 - 1952. OXFORD: OXFORD UNIV PRESS. ISSN 1541-6100
Full text not available from this repository.Abstract
Background: Intrauterine growth restriction (IUGR) is intimately linked with postnatal catch-up growth, leading to impaired lung structure and function. However, the impact of catch-up growth induced by early postnatal hyperalimentation (HA) on the lung has not been addressed to date. Objective: The aim of this study was to investigate whether prevention of HA subsequent to IUGR protects the lung from 1) deregulation of the transforming growth factor-beta(TGF-beta)/bone morphogenetic protein (BMP) pathway, 2) activation of interleukin (IL)-6 signaling, and 3) profibrotic processes. Methods: IUGR was induced in Wistar rats by isocaloric protein restriction during gestation by feeding a control (Co) or a low-protein diet with 17% or 8% casein, respectively. On postnatal day 1 (P1), litters from both groups were randomly reduced to 6 pups per dam to induce HA or adjusted to 10 pups and fed with standard diet: Co, Co with HA (Co-HA), IUGR, and IUGR with HA (IUGR-HA). Results: Birth weights in rats after IUGR were lower than in Co rats (P < 0.05). HA during lactation led to accelerated body weight gain from P1 to P23 (Co vs. Co-HA, IUGR vs. IUGR-HA; P < 0.05). At P70, prevention of HA after IUGR protected against the following: 1) activation of both TGF-beta [phosphorylated SMAD (pSMAD) 2; plasminogen activator inhibitor 1 (Pai1)] and BMP signaling [pSMAD1; inhibitor of differentiation (Id1)] compared with Co (P < 0.05) and Co or IUGR (P < 0.05) rats, respectively; 2) greater mRNA expression of interleukin (Il) 6 and Il13 (P < 0.05) as well as activation of signal transducer and activator of transcription 3 (STAT3) signaling (P < 0.05) after IUGR-HA; and 3) greater gene expression of collagen I alpha 1 and osteopontin (P < 0.05) and increased deposition of bronchial subepithelial connective tissue in IUGR-HA compared with Co and IUGR rats. Moreover, HA had a significant additive effect (P < 0.05) on the increased enhanced pause (indicator of airway resistance) in the IUGR group (P < 0.05). at P70. Conclusions: This study demonstrates a dual mechanism in IUGR-associated lung disease that is 1) IUGR-dependent and 2) HA-mediated and thereby offers new avenues to develop innovative preventive strategies for perinatal programming of adult lung diseases.
Item Type: | Journal Article | ||||||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-422642 | ||||||||||||||||||||||||||||||||
DOI: | 10.3945/jn.114.197657 | ||||||||||||||||||||||||||||||||
Journal or Publication Title: | J. Nutr. | ||||||||||||||||||||||||||||||||
Volume: | 144 | ||||||||||||||||||||||||||||||||
Number: | 12 | ||||||||||||||||||||||||||||||||
Page Range: | S. 1943 - 1952 | ||||||||||||||||||||||||||||||||
Date: | 2014 | ||||||||||||||||||||||||||||||||
Publisher: | OXFORD UNIV PRESS | ||||||||||||||||||||||||||||||||
Place of Publication: | OXFORD | ||||||||||||||||||||||||||||||||
ISSN: | 1541-6100 | ||||||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/42264 |
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