TY - JOUR T1 - The transforming growth factor-β/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J SP - 1094 LP - 1104 DO - 10.1183/09031936.00138206 VL - 29 IS - 6 AU - A. Zakrzewicz AU - F. M. Kouri AU - B. Nejman AU - G. Kwapiszewska AU - M. Hecker AU - R. Sandu AU - E. Dony AU - W. Seeger AU - R. T. Schermuly AU - O. Eickelberg AU - R. E. Morty Y1 - 2007/06/01 UR - http://erj.ersjournals.com/content/29/6/1094.abstract N2 - 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. ER -