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Dingemann, J; Doi, T; Ruttenstock, E; Puri, P.
Abnormal platelet-derived growth factor signaling accounting for lung hypoplasia in experimental congenital diaphragmatic hernia.
J Pediatr Surg. 2010; 45(10):1989-1994
Doi: 10.1016/j.jpedsurg.2010.06.014
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
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Ruttenstock Elke Maria
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- Abstract:
- Purpose: The pathogenesis of pulmonary hypoplasia in congenital diaphragmatic hernia (CDH) is not fully understood. Platelet-derived growth factor A (PDGFA) and platelet-derived growth factor receptor alpha (PDGFR alpha) play a crucial role in lung development. It has been reported that PDGF induces H(2)O(2)-production and that oxidative stress may be an important mechanism for the impaired lung development in the nitrofen rat model. We hypothesized that pulmonary expression of PDGFA and PDGFR alpha is altered in the nitrofen induced CDH model. Materials and Methods: Pregnant rats received 100 mg nitrofen or vehicle on gestational day 9 (D9) and were sacrificed on D15, D18 or D21. RNA was extracted from fetal left lungs and mRNA levels of PDGFA and PDGFR alpha were determined using real-time polymerase chain reaction. Immunohistochemistry for protein expression of PDGFA and PDGFR alpha was performed. Pulmonary H(2)O(2) was measured colorimetrically. Results: mRNA levels of PDGFR alpha at D15 (4.50 +/- 0.87) and PDGFA at D18 (2.90 +/- 1.38) were increased in the nitrofen group (P < .05). Immunohistochemistry revealed increased pulmonary expression of PDGFR alpha and PDGFA. H(2)O(2) content was significantly higher in the nitrofen group. Conclusions: Increased expression of PDGFA and PDGFR alpha suggests that pulmonary hypoplasia in the nitrofen CDH model may be owing to PDGF-induced oxidative stress during lung development. (C) 2010 Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
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Animals -
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Disease Models, Animal -
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Down-Regulation -
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Female -
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Fetal Development - drug effects
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Gene Expression Regulation, Developmental - physiology
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Hernia, Diaphragmatic - chemically induced
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Lung - abnormalities
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Morphogenesis - drug effects
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Oxidative Stress - physiology
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Phenyl Ethers -
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Platelet-Derived Growth Factor - genetics
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Pregnancy -
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RNA, Messenger - genetics
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Rats -
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Rats, Sprague-Dawley -
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Receptors, Platelet-Derived Growth Factor - physiology
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Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
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Congenital diaphragmatic Hernia
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Nitrofen
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Lung development
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PDGF
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Oxidation