Lung hypoplasia caused by nitrofen is mediated by down-regulation of thyroid transcription factor TTF-1
Lung hypoplasia caused by nitrofen is mediated by down-regulation of thyroid transcription factor TTF-1
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除草醚引起的肺发育不全是由甲状腺转录因子 TTF-1 下调介导的
DOI：
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
J. Tovar
中科院分区：
文献类型：
--
作者：
A. Losada;H. Xia;L. Migliazza;J. Diez;P. Santisteban;J. Tovar
产前接触硝芬可诱发肺发育不全和膈疝，与人类疾病非常相似，但其机制尚不清楚。甲状腺转录因子1 （TTF-1）参与肺个体发育和表面活性剂蛋白表达的调控，可能在硝芬诱导的肺发育不全中异常表达。本研究考察了硝芬对产前大鼠胎儿肺部TTF-1信使RNA （mRNA）表达的影响，以及在体内同时表达TTF-1和表面活性剂蛋白的人肺细胞系（NCI-H441）。采用northern blot分析方法，对妊娠第9.5天给予100 mg硝芬的大鼠早产儿肺和NCI-H441细胞在含10%胎牛血清的RPMI培养基中，不同时间和浓度暴露于硝芬中，检测TTF-1 mRNA的表达。与对照组相比，硝芬暴露幼鼠的TTF-1 mRNA表达降低，并且硝芬暴露导致H441细胞培养物中TTF-1表达的剂量和时间相关降低。这些结果表明，硝芬在体内和体外均能下调TTF-1。由于这干扰了肺的发育，我们可以合理地认为，该模型中的肺发育不全部分是由于致畸原的直接作用，而不是由于腹部脏器疝入胸腔的压迫。这一机制应在临床环境中加以探讨。
Abstract 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.
表面活性蛋白在大鼠胚胎肺中的表达。
DOI：
10.1165/ajrcmb.10.2.7509164
发表时间：
1994
影响因子：
6.4
作者：
Wang,J;Souza,P;Kuliszewski,M;Tanswell,AK;Post,M
通讯作者：
Post,M