Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Friedmacher, F; Gosemann, JH; Fujiwara, N; Alvarez, LA; Corcionivoschi, N; Puri, P.
Spatiotemporal alterations in Sprouty-2 expression and tyrosine phosphorylation in nitrofen-induced pulmonary hypoplasia.
J Pediatr Surg. 2013; 48(11): 2219-2225.
Doi: 10.1016/j.jpedsurg.2013.07.003
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Friedmacher Florian
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- Abstract:
- Pulmonary hypoplasia (PH) is a life-threatening condition of newborns presenting with congenital diaphragmatic hernia (CDH). Sprouty-2 functions as a key regulator of fibroblast growth factor receptor (FGFR) signalling in developing foetal lungs. It has been reported that FGFR-mediated alveolarization is disrupted in nitrofen-induced PH. Sprouty-2 knockouts show severe defects in lung morphogenesis similar to nitrofen-induced PH. Upon FGFR stimulation, Sprouty-2 is tyrosine-phosphorylated, which is essential for its physiological function during foetal lung development. We hypothesized that Sprouty-2 expression and tyrosine phosphorylation are altered in nitrofen-induced PH. Time-pregnant rats received either nitrofen or vehicle on gestation day 9 (D9). Foetal lungs were dissected on D18 and D21. Pulmonary Sprouty-2 gene and protein expression levels were analyzed by qRT-PCR, Western blotting and immunohistochemical staining. Relative mRNA expression of Sprouty-2 was significantly decreased in hypoplastic lungs without CDH (0.1050±0.01 vs. 0.3125±0.01; P<.0001) and with CDH (0.1671±0.01 vs. 0.3125±0.01; P<.0001) compared to controls on D18. Protein levels of Sprouty-2 were markedly decreased in hypoplastic lungs on D18 with decreased tyrosine phosphorylation levels on D18 and D21 detected at the molecular weight of Sprouty-2 consistent with Sprouty-2 tyrosine phosphorylation. Sprouty-2 immunoreactivity was markedly decreased in hypoplastic lungs on D18 and D21. Spatiotemporal alterations in pulmonary Sprouty-2 expression and tyrosine phosphorylation during the late stages of foetal lung development may interfere with FGFR-mediated alveolarization in nitrofen-induced PH. © 2013.
- Find related publications in this database (using NLM MeSH Indexing)
- Abnormalities, Multiple - chemically induced Abnormalities, Multiple - genetics Abnormalities, Multiple - metabolism
- Animals -
- Disease Models, Animal -
- Epithelial Cells - metabolism
- Female -
- Gene Expression Regulation, Developmental - drug effects
- Gestational Age -
- Hernia, Diaphragmatic - chemically induced Hernia, Diaphragmatic - embryology Hernia, Diaphragmatic - genetics Hernia, Diaphragmatic - metabolism
- Hernias, Diaphragmatic, Congenital -
- Lung - abnormalities Lung - embryology Lung - metabolism
- Lung Diseases - chemically induced Lung Diseases - genetics Lung Diseases - metabolism
- Nerve Tissue Proteins - biosynthesis Nerve Tissue Proteins - genetics Nerve Tissue Proteins - physiology
- Phenyl Ethers - toxicity
- Phosphotyrosine - analysis
- Pregnancy -
- Protein Processing, Post-Translational -
- Protein-Tyrosine Kinases - metabolism
- Pulmonary Alveoli - pathology
- RNA, Messenger - biosynthesis
- Random Allocation -
- Rats -
- Rats, Sprague-Dawley -
- Receptors, Fibroblast Growth Factor - physiology
- Specific Pathogen-Free Organisms -
- Find related publications in this database (Keywords)
- Sprouty-2
- Tyrosine phosphorylation
- Foetal lung development
- Nitrofen
- Pulmonary hypoplasia