title: Decreased expression of monocarboxylate transporter 1 and 4 in the branching airway epithelium of nitrofen-induced congenital diaphragmatic hernia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Florian
authors.initials: F
authors.lastname: Friedmacher
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Julia
authors.initials: J
authors.lastname: Zimmer
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland; Conway Institute of Biomolecular and Biomedical Research, School of Medicine & Medical Science, University College Dublin, Dublin, Ireland. Electronic address: prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000235:genetics; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D065630:Hernias, Diaphragmatic, Congenital / Q000139:chemically induced / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D008171:Lung Diseases / Q000196:embryology / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D038081:Organogenesis / Q000235:genetics; D010647:Phenyl Ethers; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000196:embryology / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D015415:Biomarkers; D027501:Monocarboxylic Acid Transporters; D009124:Muscle Proteins; D010647:Phenyl Ethers; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C516342:Slc16a3 protein, rat; C007350:nitrofen
keywords: Congenital diaphragmatic hernia; Lung branching morphogenesis; Monocarboxylate transporters; Nitrofen; Pulmonary hypoplasia