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SHR Neuro Cancer Cardio Lipid Metab Microb
Takahashi, H; Friedmacher, F; Fujiwara, N; Hofmann, A; Kutasy, B; Gosemann, JH; Puri, P.
Pulmonary FGF-18 gene expression is downregulated during the canalicular-saccular stages in nitrofen-induced hypoplastic lungs.
Pediatr Surg Int. 2013; 29(11): 1199-1203.
Doi: 10.1007/s00383-013-3387-4
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Friedmacher Florian
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- Abstract:
- Pulmonary hypoplasia (PH) associated with congenital diaphragmatic hernia (CDH) represents one of the major challenges in neonatal intensive care. However, the molecular pathogenesis of PH is still poorly understood. In developing fetal lungs, fibroblast growth factor 18 (FGF-18) plays a crucial role in distal airway maturation. FGF-18 knockouts show smaller lung sizes with reduced alveolar spaces and thicker interstitial mesenchymal compartments, highlighting its important function for fetal lung growth and differentiation. We hypothesized that pulmonary FGF-18 gene expression is downregulated during late gestation in nitrofen-induced hypoplastic lungs. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetuses were harvested on D18 and D21, and lungs were divided into three groups: controls, hypoplastic lungs without CDH [CDH(-)], and hypoplastic lungs with CDH [CDH(+)] (n = 24 at each time-point). Pulmonary FGF-18 gene expression levels were analyzed by qRT-PCR. Immunohistochemistry was performed to investigate FGF-18 protein expression/distribution. Relative mRNA levels of pulmonary FGF-18 gene expression were significantly decreased in CDH(-) and CDH(+) on D18 and D21 compared to controls (p < 0.05 and p < 0.01, respectively). Immunoreactivity of FGF-18 was markedly diminished in mesenchymal cells surrounding the airway epithelium on D18 and D21 compared to controls. Downregulation of FGF-18 gene expression in nitrofen-induced hypoplastic lungs suggests that decreased FGF-18 expression during the canalicular-saccular stages may interfere with saccular-alveolar differentiation and distal airway maturation resulting in PH.
- Find related publications in this database (using NLM MeSH Indexing)
- Abnormalities, Multiple - embryology Abnormalities, Multiple - genetics Abnormalities, Multiple - metabolism
- Animals -
- Disease Models, Animal -
- Down-Regulation -
- Female -
- Fibroblast Growth Factors - biosynthesis Fibroblast Growth Factors - genetics
- Gene Expression Regulation, Developmental -
- Immunohistochemistry -
- Lung - abnormalities Lung - embryology Lung - metabolism
- Lung Diseases - embryology Lung Diseases - genetics Lung Diseases - metabolism
- Organogenesis -
- Phenyl Ethers - toxicity
- Pregnancy -
- Pregnancy, Animal -
- RNA - genetics
- Rats -
- Rats, Sprague-Dawley -
- Reverse Transcriptase Polymerase Chain Reaction -
- Find related publications in this database (Keywords)
- Fibroblast growth factor 18
- Congenital diaphragmatic hernia
- Pulmonary hypoplasia
- Nitrofen