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Gosemann, JH; Doi, T; Kutasy, B; Friedmacher, F; Dingemann, J; Puri, P.
Alterations of peroxisome proliferator-activated receptor γ and monocyte chemoattractant protein 1 gene expression in the nitrofen-induced hypoplastic lung.
J Pediatr Surg. 2012; 47(5): 847-851.
Doi: 10.1016/j.jpedsurg.2012.01.038
Web of Science
PubMed
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- Co-authors Med Uni Graz
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Friedmacher Florian
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Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in normal lung development. Peroxisome proliferator-activated receptor γ messenger RNA (mRNA) is detectable at 18 days of gestation in fetal rat lungs, and levels peak just before birth. Peroxisome proliferator-activated receptor γ agonists are reported to stimulate lung development, whereas inhibition of PPARγ disrupts postnatal lung maturation. Monocyte chemoattractant protein 1 (MCP-1), which is inhibited by PPARγ, is reported to disrupt late lung morphogenesis. This study was designed to investigate the hypothesis that PPARγ expression is downregulated and that MCP-1 expression is upregulated during the late stages of lung development in nitrofen-induced hypoplastic lungs.
Pregnant rats were treated with nitrofen or vehicle on D9. RNA was extracted from fetal lungs (D18 and D21), and relative mRNA expression levels of PPARγ and MCP-1 were determined by reverse transcriptase-polymerase chain reaction. Immunohistochemistry was performed to evaluate protein expression/distribution of PPARγ and MCP-1.
Relative mRNA expression levels of PPARγ were significantly downregulated in the nitrofen group compared with controls on D21, whereas MCP-1 levels were upregulated. Immunohistochemical study showed markedly decreased PPARγ and increased MCP-1 immunoreactivity in the nitrofen-induced hypoplastic lungs compared with controls on gestational day 21.
Altered pulmonary gene expression of PPARγ and MCP-1 during late gestation may impair lung development and maturation, contributing to pulmonary hypoplasia in the nitrofen-induced congenital diaphragmatic hernia model.
Copyright © 2012 Elsevier Inc. All rights reserved.
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Animals -
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Biological Markers - metabolism
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Chemokine CCL2 - metabolism
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Disease Models, Animal -
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Down-Regulation -
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Female -
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Hernia, Diaphragmatic - chemically induced Hernia, Diaphragmatic - complications Hernia, Diaphragmatic - embryology Hernia, Diaphragmatic - metabolism
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Hernias, Diaphragmatic, Congenital -
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Immunohistochemistry -
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Lung - abnormalities Lung - embryology Lung - metabolism
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Lung Diseases - chemically induced Lung Diseases - complications Lung Diseases - embryology Lung Diseases - metabolism
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PPAR gamma - metabolism
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Phenyl Ethers -
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Pregnancy -
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Random Allocation -
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Rats -
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Rats, Sprague-Dawley -
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Reverse Transcriptase Polymerase Chain Reaction -
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Up-Regulation -
- Find related publications in this database (Keywords)
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PPAR gamma
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Nitrofen
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MCP-1
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Hypoplastic lung
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Congenital diaphragmatic
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hernia