Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Takahashi, H; Friedmacher, F; Fujiwara, N; Hofmann, A; Takahashi, T; Puri, P.
Downregulation of p300 gene expression in airway mesenchyme of nitrofen-induced hypoplastic lungs.
Pediatr Surg Int. 2014; 30(4): 431-435.
Doi: 10.1007/s00383-014-3466-1
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Friedmacher Florian
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- Abstract:
- Congenital diaphragmatic hernia (CDH) is a relatively common developmental abnormality causing life-threatening respiratory distress at birth. The nitrofen model has been widely used to investigate the pathogenesis of hypoplastic lungs associated with CDH. Embryos lacking p300 and CBP genes are significantly smaller in lung formation. We hypothesized that pulmonary gene expression of p300 and CBP is downregulated during late gestation in the nitrofen-induced CDH model. Time-pregnant rats were treated with either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were harvested on D18 and D21 (n = 8 at each time point). Pulmonary gene expression of p300 and CBP was analyzed by quantitative real-time PCR. Immunohistochemistry was performed to investigate expression and localization of pulmonary p300 and CBP proteins. Relative mRNA expression levels of p300 were significantly decreased in nitrofen-induced hypoplastic lungs on D18 compared to controls (3.00 ± 0.20 vs. 3.76 ± 0.14; p = 0.0039), while CBP levels were not altered. p300 immunoreactivity was markedly diminished in surrounding mesenchymal compartments and nuclei of proximal and distal airway cells, while CBP expression was not altered. Downregulation of p300 gene expression during the early canalicular stage may disrupt epithelial-mesenchymal signaling interactions, contributing to the development of hypoplastic lungs in the nitrofen-induced CDH model.
- Find related publications in this database (using NLM MeSH Indexing)
- Abnormalities, Multiple - chemically induced Abnormalities, Multiple - genetics
- Animals -
- Down-Regulation -
- E1A-Associated p300 Protein - biosynthesis E1A-Associated p300 Protein - genetics
- Gene Expression Regulation -
- Hernias, Diaphragmatic, Congenital - chemically induced Hernias, Diaphragmatic, Congenital - genetics
- Lung - abnormalities
- Lung Diseases - chemically induced Lung Diseases - genetics
- Membrane Proteins - biosynthesis Membrane Proteins - genetics
- Mesoderm - metabolism
- Phenyl Ethers -
- Phosphoproteins - biosynthesis Phosphoproteins - genetics
- Rats -
- Rats, Sprague-Dawley -
- Find related publications in this database (Keywords)
- p300
- Congenital diaphragmatic hernia
- Pulmonary hypoplasia
- Nitrofen