Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zakrzewicz, A; Kouri, FM; Nejman, B; Kwapiszewska, G; Hecker, M; Sandu, R; Dony, E; Seeger, W; Schermuly, RT; Eickelberg, O; Morty, RE.
The transforming growth factor-beta/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension.
Eur Respir J. 2007; 29(6): 1094-1104.
Doi: 10.1183/09031936.00138206
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- Kwapiszewska-Marsh Grazyna
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Disease Models, Animal -
- Hypertension, Pulmonary - metabolism Hypertension, Pulmonary - pathology
- Lung - pathology
- Models, Biological -
- Monocrotaline - pharmacology
- Mutation -
- Pulmonary Artery - pathology
- Rats -
- Receptors, Transforming Growth Factor beta - metabolism
- Signal Transduction -
- Smad2 Protein - genetics
- Smad3 Protein - metabolism
- Transforming Growth Factor beta - metabolism
- Find related publications in this database (Keywords)
- apoptosis
- monocrotaline
- pulmonary artery smooth muscle cells
- transforming growth factor-beta
- vascular remodelling