Decreased expression of monocarboxylate transporter 1 and 4 in the branching airway epithelium of nitrofen-induced congenital diaphragmatic hernia

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• 作者：Toshiaki Takahashi^a ; Florian Friedmacher^a ; Julia Zimmer^a ; Prem Puri^a ; ^b ; ^{prem.puri@ncrc.ie" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Monocarboxylate transporters ; Lung branching morphogenesis ; Pulmonary hypoplasia ; Congenital diaphragmatic hernia ; Nitrofen
• 刊名：Journal of Pediatric Surgery
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：51
• 期：6
• 页码：896-899
• 全文大小：644 K

文摘

Monocarboxylate transporters (MCTs) are crucial for the maintenance of intracellular pH homeostasis in developing fetal lungs. MCT1/4 is strongly expressed by epithelial airway cells throughout lung branching morphogenesis. Functional inhibition of MCT1/4 in fetal rat lung explants has been shown to result in airway defects similar to pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). We hypothesized that pulmonary expression of MCT1/4 is decreased during lung branching morphogenesis in the nitrofen model of CDH-associated PH.

Methods

Timed-pregnant rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were harvested on D15, D18, and D21, and divided into control and nitrofen-exposed group. Pulmonary gene expression levels of MCT1/4 were analyzed by qRT-PCR. Immunofluorescence staining for MCT1/4 was combined with E-cadherin in order to evaluate protein expression in branching airway tissue.

Results

Relative mRNA levels of MCT1/4 were significantly reduced in lungs of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls. Confocal laser scanning microscopy confirmed markedly decreased immunofluorescence of MCT1/4 in distal bronchial and primitive alveolar epithelium of nitrofen-exposed fetuses on D15, D18, and D21 compared to controls.

Conclusion

Decreased expression of MCT1/4 in distal airway epithelium may disrupt lung branching morphogenesis and thus contribute to the development of PH in the nitrofen-induced CDH model.