title: Increased expression of activated pSTAT3 and PIM-1 in the pulmonary vasculature of experimental congenital diaphragmatic hernia.
abstract: OBJECTIVE
  Signal transducer and activator of transcription (STAT) protein family (STAT1-6) regulates diverse cellular processes. Recently, the isoform STAT3 has been implicated to play a central role in the pathogenesis of pulmonary hypertension (PH). In human PH activated STAT3 (pSTAT3) was shown to directly trigger expression of the provirus integration site for Moloney murine leukemia virus (Pim-1), which promotes proliferation and resistance to apoptosis in SMCs. We designed this study to investigate the hypothesis that pSTAT3 and Pim-1 pulmonary vascular expression is increased in nitrofen-induced CDH.
  
  
  METHODS
  Pregnant rats were exposed to nitrofen or vehicle on D9.5. Fetuses were sacrificed on D21 and divided into nitrofen (n=16) and control group (n=16). QRT-PCR, western blotting, and confocal-immunofluorescence were performed to determine pulmonary gene and protein expression levels of pSTAT3 and Pim-1.
  
  
  RESULTS
  Pulmonary Pim-1 gene expression was significantly increased in the CDH group compared to controls. Western blotting and confocal-microscopy confirmed increased pulmonary protein expression of Pim-1 and increased activation of pSTAT3 in CDH lungs compared to controls.
  
  
  CONCLUSIONS
  Markedly increased gene and protein expression of Pim-1 and activated pSTAT3 in the pulmonary vasculature of nitrofen-induced CDH lungs suggest that pSTAT3 and Pim-1 are important mediators of PH in nitrofen-induced CDH.
authors: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors: Alejandro D
authors: AD
authors: Hofmann
authors: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors: Toshiaki
authors: T
authors: Takahashi
authors: 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.
authors: Johannes
authors: J
authors: Duess
authors: National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin, Ireland.
authors: Jan-Hendrik
authors: JH
authors: Gosemann
authors: 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: Prem
authors: P
authors: Puri
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D018507:Gene Expression Regulation, Developmental; D065630:Hernias, Diaphragmatic, Congenital / Q000150:complications / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000196:embryology / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000196:embryology / Q000378:metabolism*; D010647:Phenyl Ethers; D011247:Pregnancy; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010647:Phenyl Ethers; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C496637:Pim1 protein, rat; D051573:Proto-Oncogene Proteins c-pim-1; C007350:nitrofen
keywords: Congenital diaphragmatic hernia; Nitrofen; Pim-1; Pulmonary hypertension; STAT3; Vascular remodeling