Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation
Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation
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DOI：
10.1152/ajplung.00342.2004
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发表时间：
2005-07-01
影响因子：
4.9
通讯作者：
Kitterman, JA
中科院分区：
文献类型：
--
作者：
Chapin, CJ;Ertsey, R;Kitterman, JA
Chapin，Cheryl J.，Robert Ertsey、Jyoji Yoshizawa、Akihiko Hara、Lourenco Sbragia、John J. Greer和Joseph A.先天性腹股沟疝、气管闭塞、甲状腺转录因子-1和胎儿肺上皮成熟。美国生理学杂志肺细胞分子生理学289：L44-L52，2005年。首次发表于2005年3月11日; doi：10.1152/ajplung。00342.2004.-先天性腹股沟疝（CDH）的发生率与1：2，500的人类出生率相似，并且具有高发病率和死亡率，主要是由于肺发育不全和肺动脉高压。在实验动物中，气管闭塞（TO）使肺扩张并增加肺生长和肺泡I型细胞成熟，但减少表面活性剂组分并降低肺泡II型细胞密度。我们研究了CDH和CDH+TO对胎鼠肺生长和成熟的影响。为了诱导CDH，我们在妊娠9.5天时给母鼠施用除草醚（100 mg）。我们比较了患有CDH、CDH+TO和暴露于除草醚但未患有CDH的胎儿的肺。CDH可降低肺湿重（P < 0.0001）和同侧肺DNA含量（P < 0.05）。CDH+TO显著增加双侧肺湿重; DNA含量介于CDH和NC之间。为了评估对远端肺上皮的影响，我们检测了表面活性物质mRNA和蛋白水平、I型和II型细胞特异性标志物（分别为RTI 40和RTII 70）以及转录调节因子甲状腺转录因子-1（TTF-1）。CDH所致肺膨胀减轻时SP-C mRNA和TTF-1蛋白表达增加，RTI 40降低（均P < 0.05）。肺扩张增加（由于CDH+TO）降低SP mRNA和pro-SP-C和TTF-1蛋白的表达，并增加RTI 40（mRNA和蛋白;均P < 0.05）的表达。我们的结论是，CDH + TO部分逆转CDH的影响，它纠正了肺发育不良和恢复I型细胞分化，但对II型细胞中的SP表达产生不利影响。这些作用可能通过TTF-1表达的变化介导。
Chapin, Cheryl J., Robert Ertsey, Jyoji Yoshizawa, Akihiko Hara, Lourenco Sbragia, John J. Greer, and Joseph A. Kitter-man. Congenital diaphragmatic hernia, tracheal occlusion, thyroid transcription factor-1, and fetal pulmonary epithelial maturation. Am J Physiol Lung Cell Mol Physiol 289: L44-L52, 2005. First published March 11, 2005; doi:10.1152/ajplung. 00342.2004.-Congenital diaphragmatic hernia (CDH) occurs in similar to 1:2,500 human births and has high morbidity and mortality rates, primarily due to pulmonary hypoplasia and pulmonary hypertension. Tracheal occlusion ( TO), in experimental animals, distends lungs and increases lung growth and alveolar type I cell maturation but decreases surfactant components and reduces alveolar type II cell density. We examined effects of CDH and CDH+TO on lung growth and maturation in fetal rats. To induce CDH, we administered nitrofen (100 mg) to dams at 9.5 days of gestation. We compared lungs from fetuses with CDH, CDH+TO, and those exposed to nitrofen without CDH. CDH decreased lung wet weight bilaterally (P < 0.0001) and DNA content in lung ipsilateral to CDH (P < 0.05). CDH+TO significantly increased lung wet weights bilaterally; DNA content was intermediate between CDH and NC. To evaluate effects on the distal pulmonary epithelium, we examined surfactant mRNA and protein levels, type I and II cell-specific markers (RTI40 and RTII70, respectively), and transcriptional regulator thyroid transcription factor-1 (TTF-1). Decreased lung distension ( due to CDH) increased SP-C mRNA and TTF-1 protein expression and reduced RTI40 (P < 0.05 for all). Increased lung distension ( due to CDH+TO) reduced expression of SP mRNAs and pro-SP-C and TTF-1 proteins and enhanced expression of RTI40 ( mRNA and protein; P < 0.05 for all). We conclude that CDH + TO partially reverses effects of CDH; it corrects the pulmonary hypoplasia and restores type I cell differentiation but adversely affects SP expression in type II cells. These effects may be mediated through changes in TTF-1 expression.