Up-regulation of COUP-TFII gene expression in the nitrofen-induced hypoplastic lung.
OBJECTIVE
Recent studies have suggested that the retinoid signaling pathway (RSP) is inhibited in the nitrofen-induced hypoplastic lung. The exact mechanism by which nitrofen acts in the RSP remains unclear. Targeted ablation of COUP-TFII, a gene encoding a transfactor regulated by the RSP, has been shown to cause Bochdalek-type congenital diaphragmatic hernia. It has been shown that COUP-TFII has 2 main roles in the RSP, (i) repressing the RSP by directly sequestering retinoid X receptors, thereby preventing heterodimerization to retinoid acid receptors and inhibiting gene transcription, and (ii) modulating the transcriptional activity of GATA proteins. We designed this study to investigate the gene expression of COUP-TFII in the nitrofen-induced hypoplastic lung.


METHODS
Pregnant rats were exposed to either olive oil or 100 mg of nitrofen on day 9 of gestation. Fetuses were harvested and lungs were dissected on day 15 (D15), D18, and D21 and divided into 2 groups: control (n = 9) and nitrofen (n = 9). Real-time reverse transcription-polymerase chain reaction was performed to evaluate the relative mRNA levels of COUP-TFII expression in the hypoplastic lung.


RESULTS
The relative mRNA levels of COUP-TFII at D15 was significantly increased in the nitrofen group (0.76 +/- 0.53) compared to controls (0.45 +/- 0.05) (P < .01). The expression levels of COUP-TFII at D18 and D21 were not significantly different between the nitrofen group and controls.


CONCLUSIONS
Our results provide evidence for the first time that the pulmonary gene expression of COUP-TFII is up-regulated in the early stages of lung development in the nitrofen-induced hypoplastic lung. We speculate that up-regulation of COUP-TFII gene expression during the stage of branching lung morphogenesis may cause pulmonary hypoplasia by repressing RSP.
Doi
Takashi
T
The Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland.
Sugimoto
Kaoru
K
Puri
Prem
P
D000818:Animals; D051837:COUP Transcription Factor II / Q000235:genetics*; D008168:Lung / Q000002:abnormalities*; D010647:Phenyl Ethers / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D012176:Retinoids / Q000502:physiology; D015398:Signal Transduction; D015854:Up-Regulation
D051837:COUP Transcription Factor II; C497588:Nr2f2 protein, rat; D010647:Phenyl Ethers; D012176:Retinoids; C007350:nitrofen