Lung hypoplasia caused by nitrofen is mediated by down-regulation of thyroid transcription factor TTF-1
| Autor: | Pilar Santisteban, Huimin Xia, A Losada, L Migliazza, Juan A. Tovar, Juan A. Diez-Pardo |
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| Rok vydání: | 1999 |
| Předmět: |
endocrine system
medicine.medical_specialty Thyroid Nuclear Factor 1 Thyroid Transcription Factor 1 Down-Regulation Rats Sprague-Dawley chemistry.chemical_compound Pregnancy Internal medicine Tumor Cells Cultured medicine Respiratory muscle Animals Humans RNA Messenger Lung Hernia Diaphragmatic Homeodomain Proteins Fetus business.industry Phenyl Ethers Nuclear Proteins General Medicine respiratory system medicine.disease Nitrofen Hypoplasia Rats medicine.anatomical_structure Endocrinology chemistry Pediatrics Perinatology and Child Health Female Surgery Hernias Diaphragmatic Congenital business Fetal bovine serum Transcription Factors |
| Zdroj: | Pediatric Surgery International. 15:188-191 |
| ISSN: | 1437-9813 0179-0358 |
| DOI: | 10.1007/s003830050551 |
| Popis: | Prenatal exposure to nitrofen induces lung hypoplasia and diaphragmatic hernias very similar to those in human disease, but the mechanisms are still unknown. Thyroid transcription factor 1 (TTF-1) is involved in lung ontogeny and regulation of the expression of surfactant proteins, and is likely abnormally expressed in nitrofen-induced lung hypoplasia. This study examines the effect of nitrofen on TTF-1 messenger RNA (mRNA) expression in the lungs of prenatal rat fetuses and a human lung-cell line (NCI-H441) that expresses both TTF-1 and surfactant proteins in vivo. Lungs from preterm fetuses harvested from rats with 100 mg nitrofen on gestational day 9.5 and NCI-H441 cells maintained in RPMI medium containing 10% fetal bovine serum and exposed to nitrofen for different times and concentrations were assayed for TTF-1 mRNA by northern blot analysis. mRNA for TTF-1 was decreased in nitrofen-exposed pups in comparison with controls, and exposure to nitrofen caused a dose- and time-related decrease in TTF-1 expression in H441 cell cultures. These results indicate that nitrofen downregulates TTF-1 both in vivo and in vitro. Since this interferes with lung development, it is reasonable to accept that lung hypoplasia in this model is in part due to the direct effect of the teratogen rather than to compression by the abdominal viscera herniated into the thorax. This mechanism should be explored in the clinical setting. |
| Databáze: | OpenAIRE |
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