RT Journal Article
SR Electronic
T1 The transforming growth factor-β/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1094
OP 1104
DO 10.1183/09031936.00138206
VO 29
IS 6
A1 A. Zakrzewicz
A1 F. M. Kouri
A1 B. Nejman
A1 G. Kwapiszewska
A1 M. Hecker
A1 R. Sandu
A1 E. Dony
A1 W. Seeger
A1 R. T. Schermuly
A1 O. Eickelberg
A1 R. E. Morty
YR 2007
UL http://erj.ersjournals.com/content/29/6/1094.abstract
AB Mutations in genes encoding members of the transforming growth factor (TGF)-β superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-β/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH. Expression of the TGF-β 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-β 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-β receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-β signalling and TGF-β-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-β/Smad2,3 signalling axis is functionally impaired in monocrotaline-treated rodents with severe pulmonary arterial hypertension, underscoring the potential importance of transforming growth factor-β/Smad2,3 signalling in the onset or development of pulmonary arterial hypertension.