title: Pulmonary FGF9 gene expression is downregulated during the pseudoglandular stage in nitrofen-induced hypoplastic lungs.
abstract: BACKGROUND
  The pathogenesis of pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH) remains unclear. Fibroblast growth factor 9 (FGF9) is an essential component of the gene network that regulates lung development. FGF9 knockouts exhibit disrupted mesenchymal proliferation and reduced airway branching. The authors hypothesized that pulmonary FGF9 gene expression is downregulated during the pseudoglandular stage in nitrofen-induced hypoplastic lungs.
  
  
  METHODS
  Pregnant rats received either nitrofen or vehicle on gestational day 9 (D9). Fetal lungs were dissected on D15 and D18, and were divided into controls, hypoplastic lungs with CDH (CDH+) and hypoplastic lungs without CDH (CDH-). Pulmonary FGF9 gene expression levels were analyzed by quantitative real-time polymerase chain reaction. Immunohistochemistry was performed to investigate FGF9 protein expression/distribution.
  
  
  RESULTS
  Relative messenger RNA levels of FGF9 were significantly decreased on D15 in hypoplastic lungs compared with controls (p < 0.01), and on D18 in CDH+ and CDH- compared with controls (p< 0.05, respectively). Immunoreactivity of FGF9 was markedly diminished in mesothelium and distal airway epithelium on D15 and decreased in overall intensity on D18 in hypoplastic lungs compared with controls.
  
  
  CONCLUSIONS
  Downregulation of FGF9 gene expression during the pseudoglandular stage may cause pulmonary hypoplasia in the nitrofen model by decreasing distal airway epithelial and mesenchymal proliferation throughout the branching morphogenesis.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Hiromizu
authors.initials: H
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: Naho
authors.initials: N
authors.lastname: Fujiwara
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hofmann
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics*; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000235:genetics*; D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000235:genetics / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D008168:Lung / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D010647:Phenyl Ethers / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C496461:Fgf9 protein, rat; D051525:Fibroblast Growth Factor 9; D010647:Phenyl Ethers; C007350:nitrofen