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Ruttenstock, E; Doi, T; Dingemann, J; Puri, P.
Insulinlike growth factor receptor type 1 and type 2 are downregulated in the nitrofen-induced hypoplastic lung.
J Pediatr Surg. 2010; 45(6):1349-1353
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Autor/innen der Med Uni Graz:
Zani-Ruttenstock Elke Maria
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Abstract:
Purpose: In congenital diaphragmatic hernia (CDH), high mortality rates are attributed to severe pulmonary hypoplasia. The insulinlike growth factor receptor type 1 (IGF-1R) and type 2 (IGF-2R) play a critical role in the alveologenesis during lung development. The IGF-1R null mutation mice die after birth because of respiratory failure. The IGF-2R knockout mice showed retarded lungs with poorly formed alveoli. We hypothesized that IGF-1R and IGF-2R gene expression levels are downregulated in the nitrofen-induced CDH model. Methods: Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9.5 (D9.5) of gestation. Fetuses were harvested on D18 and D21 and divided into control and nitrofen groups. Relative messenger RNA (mRNA) levels of IGF-1R and IGF-2R were determined using real time reverse transcription polymerase chain reaction. Immunohistochemistry was performed to determine protein expression. Results: Relative levels of IGF-1R mRNA were significantly decreased in the nitrofen group (2.91 +/- 0.81) on D21 compared to controls (5.29 +/- 2.59) (P < .05). Expression levels of IGF-2R mRNA on D21 were also significantly decreased in nitrofen group (1.76 +/- 0.49) compared to controls (3.59 +/- 2.45) (P < .05). Immunohistochemistry performed on D21 showed decreased IGF-1R and also IGF-2R expression in nitrofen group. Conclusion: Downregulation of IGF-1R and IGF-2R gene expression may interfere with normal alveologenesis causing pulmonary hypoplasia in the nitrofen-induced CDH model. (C) 2010 Elsevier Inc. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Disease Models, Animal -
Down-Regulation -
Female -
Gene Expression Regulation, Developmental -
Immunohistochemistry -
Lung - abnormalities Lung - embryology Lung - metabolism
Lung Diseases - embryology Lung Diseases - genetics Lung Diseases - metabolism
Phenyl Ethers - toxicity
Pregnancy -
RNA, Messenger - biosynthesis RNA, Messenger - genetics
Rats -
Rats, Sprague-Dawley -
Receptor, IGF Type 1 - biosynthesis Receptor, IGF Type 1 - genetics
Receptor, IGF Type 2 - biosynthesis Receptor, IGF Type 2 - genetics
Reverse Transcriptase Polymerase Chain Reaction -

Find related publications in this database (Keywords)
IGF-1R
IGF-2R
Nitrofen
Hypoplastic lung
Congenital diaphragmatic hernia
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