title: Increased pulmonary vascular expression of receptor for advanced glycation end products (RAGE) in experimental congenital diaphragmatic hernia.
abstract: OBJECTIVE
  Persistent pulmonary hypertension (PH) continues to be a major cause of high mortality in congenital diaphragmatic hernia (CDH). The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin protein family. Recently, RAGE has been implicated in mediating pulmonary arterial smooth muscle cell proliferation and vascular remodeling in experimental PH. RAGE has been reported to be highly upregulated in lung tissue of patients with severe PH. We designed this study to investigate the hypothesis that RAGE expression is increased in nitrofen-induced CDH.
  
  
  METHODS
  Pregnant rats were exposed to nitrofen or vehicle on D9. Fetuses were sacrificed on D21 and divided into nitrofen (n=16) and control group (n=16). Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed.
  
  
  RESULTS
  Pulmonary RAGE gene expression levels were significantly increased in nitrofen-induced CDH compared to controls (p<0.003). Western blotting and confocal microscopy revealed increased pulmonary RAGE protein expression in CDH compared to controls.
  
  
  CONCLUSIONS
  This study provides striking evidence of increased gene and protein expression of RAGE in the pulmonary vasculature of nitrofen-induced CDH, suggesting that increased expression of RAGE may play a role in the pathogenesis of PH in nitrofen-induced CDH.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Hofmann
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: 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: Jan-Hendrik
authors.initials: JH
authors.lastname: Gosemann
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland; School of Medicine and Medical Science and Conway Institute of Biomedical Research, University College Dublin, Ireland. Electronic address: prem.puri@ncrc.ie.
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004247:DNA / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006548:Hernia, Diaphragmatic / Q000139:chemically induced; D065630:Hernias, Diaphragmatic, Congenital / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D004247:DNA
keywords: CDH; Nitrofen; Pulmonary hypertension; RAGE; Vascular remodeling