Source:http://linkedlifedata.com/resource/pubmed/id/17392319
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2007-6-1
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pubmed:abstractText |
Mutations in genes encoding members of the transforming growth factor (TGF)-beta superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-beta/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH. Expression of the TGF-beta signalling machinery was assessed in the lungs and kidneys of MCT-treated rodents with severe PAH by semi-quantitative reverse-transcription (RT)-PCR, real-time RT-PCR and immunoblotting. TGF-beta signalling was assessed in the lungs and in pulmonary artery smooth muscle cells (PASMC) from MCT-treated rodents by Smad2 phosphorylation, expression of the connective tissue growth factor gene, activation of the serpine promoter in a luciferase reporter system and by the induction of apoptosis. The expression of type1 TGF-beta receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-beta signalling and TGF-beta-induced apoptosis, were dramatically reduced in the lungs and PASMC, but not the kidneys, of MCT-treated rodents that developed severe PAH. The current data indicate that the transforming growth factor-beta/Smad2,3 signalling axis is functionally impaired in monocrotaline-treated rodents with severe pulmonary arterial hypertension, underscoring the potential importance of transforming growth factor-beta/Smad2,3 signalling in the onset or development of pulmonary arterial hypertension.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Madh2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Madh3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Monocrotaline,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0903-1936
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1094-104
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pubmed:dateRevised |
2007-10-15
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pubmed:meshHeading |
pubmed-meshheading:17392319-Animals,
pubmed-meshheading:17392319-Apoptosis,
pubmed-meshheading:17392319-Disease Models, Animal,
pubmed-meshheading:17392319-Hypertension, Pulmonary,
pubmed-meshheading:17392319-Lung,
pubmed-meshheading:17392319-Models, Biological,
pubmed-meshheading:17392319-Monocrotaline,
pubmed-meshheading:17392319-Mutation,
pubmed-meshheading:17392319-Pulmonary Artery,
pubmed-meshheading:17392319-Rats,
pubmed-meshheading:17392319-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:17392319-Signal Transduction,
pubmed-meshheading:17392319-Smad2 Protein,
pubmed-meshheading:17392319-Smad3 Protein,
pubmed-meshheading:17392319-Transforming Growth Factor beta
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pubmed:year |
2007
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pubmed:articleTitle |
The transforming growth factor-beta/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension.
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pubmed:affiliation |
Department of Internal Medicine, University of Giessen Lung Center, Giessen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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