Universität zu Köln

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

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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
Creators:	Creators Email ORCID ORCID Put Code Alcazar, Miguel Angel Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinger, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Oestreicher, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Vohlen, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Plank, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED
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
Uncontrolled Keywords:	Keywords Language MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS; DEVELOPMENTAL ORIGINS; BIRTH-WEIGHT; FETAL-GROWTH; CHILDREN; ASTHMA; IMPACT; RETARDATION; EXPRESSION; FIBROSIS Multiple languages Nutrition & Dietetics Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42264