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ANG-1 TIE-2 and BMPR signalling defects are not seen in the nitrofen model of pulmonary hypertension and congenital diaphragmatic hernia.

AbstractBACKGROUND:
Pulmonary hypertension (PH) is a lethal disease that is associated with characteristic histological abnormalities of the lung vasculature and defects of angiopoetin-1 (ANG-1), TIE-2 and bone morphogenetic protein receptor (BMPR)-related signalling. We hypothesized that if these signalling defects cause PH generically, they will be readily identifiable perinatally in congenital diaphragmatic hernia (CDH), where the typical pulmonary vascular changes are present before birth and are accompanied by PH after birth.
METHODS:
CDH (predominantly left-sided, LCDH) was created in Sprague-Dawley rat pups by e9.5 maternal nitrofen administration. Left lungs from normal and LCDH pups were compared at fetal and postnatal time points for ANG-1, TIE-2, phosphorylated-TIE-2, phosphorylated-SMAD1/5/8 and phosphorylated-ERK1/2 by immunoprecipitation and Western blotting of lung protein extracts and by immunohistochemistry on lung sections.
RESULTS:
In normal lung, pulmonary ANG-1 protein levels fall between fetal and postnatal life, while TIE-2 levels increase. Over the corresponding time period, LCDH lung retained normal expression of ANG-1, TIE-2, phosphorylated-TIE-2 and, downstream of BMPR, phosphorylated-SMAD1/5/8 and phosphorylated-p44/42.
CONCLUSION:
In PH and CDH defects of ANG-1/TIE-2/BMPR-related signalling are not essential for the lethal vasculopathy.
AuthorsHarriet Jane Corbett, Marilyn Gwen Connell, David Garth Fernig, Paul Damion Losty, Edwin Chitran Jesudason
JournalPloS one (PLoS One) Vol. 7 Issue 4 Pg. e35364 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22539968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiopoietin-1
  • Phenyl Ethers
  • Smad1 Protein
  • Smad5 Protein
  • Smad8 Protein
  • Receptor, TIE-2
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Bone Morphogenetic Protein Receptors
  • nitrofen
Topics
  • Angiopoietin-1 (metabolism)
  • Animals
  • Animals, Newborn
  • Bone Morphogenetic Protein Receptors (metabolism)
  • Disease Models, Animal
  • Female
  • Hernia, Diaphragmatic (chemically induced, metabolism, pathology)
  • Hernias, Diaphragmatic, Congenital
  • Hypertension (metabolism, pathology)
  • Lung (metabolism, pathology)
  • Mitogen-Activated Protein Kinase 1 (metabolism)
  • Mitogen-Activated Protein Kinase 3 (metabolism)
  • Phenyl Ethers (toxicity)
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, TIE-2 (metabolism)
  • Signal Transduction
  • Smad1 Protein (metabolism)
  • Smad5 Protein (metabolism)
  • Smad8 Protein (metabolism)

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