The transforming growth factor-beta/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension.
Eur Respir J
; 29(6): 1094-104, 2007 Jun.
Article
in En
| MEDLINE
| ID: mdl-17392319
ABSTRACT
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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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta
/
Smad2 Protein
/
Smad3 Protein
/
Mutation
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Eur Respir J
Year:
2007
Document type:
Article
Affiliation country:
Germany