title: Lower NPAS3 expression during the later stages of abnormal lung development in rat congenital diaphragmatic hernia.
abstract: OBJECTIVE
  Congenital diaphragmatic hernia (CDH) is characterized by a developmental defect in the diaphragm, pulmonary hypoplasia and pulmonary hypertension. NPAS3 is a PAS domain transcription factor regulating Drosophila tracheogenesis. NPAS3 null mice develop pulmonary hypoplasia in utero and die after birth due to respiratory failure. We aimed to evaluate NPAS3 expression during normal and abnormal lung development due to CDH.
  
  
  METHODS
  CDH was induced by administering 100 mg/ml nitrofen to time-pregnant dams on embryonic day (E) 9 of gestation. Lungs were isolated on E15, E18 and E21 and NPAS3 localization was determined by immunohistochemistry and quantified using Western blotting.
  
  
  RESULTS
  We found that only E21 hypoplastic CDH lungs have reduced expression of NPAS3 in the terminal saccules. Western blotting confirmed the down-regulation of NPAS3 protein in the nitrofen-induced hypoplastic lungs.
  
  
  CONCLUSIONS
  We demonstrate for the first time that nitrofen-induced hypoplastic CDH lungs have reduced NPAS3 expression in the terminal saccules during the later stages of abnormal lung development. Our findings suggest that NPAS3 is associated with pulmonary hypoplasia in CDH.
authors: Division of Pediatric Surgery, Departments of Surgery, Pediatrics and Child Health and Physiology and Pathophysiology (Adjunct), University of Manitoba and Children's Hospital Research Institute of Manitoba, Biology of Breathing Theme, AE402-840 Sherbrook Street, Winnipeg, MB, R3A 1R9, Canada.
authors: Patrícia
authors: P
authors: Pereira-Terra
authors: Ramin
authors: R
authors: Kholdebarin
authors: Meghan
authors: M
authors: Higgins
authors: Barbara M
authors: BM
authors: Iwasiow
authors: Jorge
authors: J
authors: Correia-Pinto
authors: Richard
authors: R
authors: Keijzer
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015153:Blotting, Western; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D065630:Hernias, Diaphragmatic, Congenital / Q000196:embryology* / Q000235:genetics*; D008168:Lung / Q000002:abnormalities / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C516513:Npas4 protein, rat