ERJ
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Published online before print March 28, 2007, 10.1183/09031936.00138206
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Permissions
Right arrowRequest Permissions
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (5)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zakrzewicz, A.
Right arrow Articles by Morty, R. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zakrzewicz, A.
Right arrow Articles by Morty, R. E.
Eur Respir J 2007; 29:1094-1104
Copyright ©ERS Journals Ltd 2007

The transforming growth factor-ß/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension

A. Zakrzewicz, F. M. Kouri, B. Nejman, G. Kwapiszewska, M. Hecker, R. Sandu, E. Dony, W. Seeger, R. T. Schermuly, O. Eickelberg and R. E. Morty

Dept of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Giessen, Germany.

CORRESPONDENCE: R. E. Morty, Dept of Internal Medicine, University of Giessen Lung Center, Justus Liebig University, Aulweg 123 (Raum 6-11), D-35392 Giessen, Germany. Fax: 49 6419942308. E-mail: rory.morty{at}innere.med.uni-giessen.de

Keywords: Apoptosis, monocrotaline, pulmonary artery smooth muscle cells, transforming growth factor-ß, vascular remodelling

Received: October 24, 2006
Accepted March 14, 2007

Mutations in genes encoding members of the transforming growth factor (TGF)-ß superfamily have been identified in idiopathic forms of pulmonary arterial hypertension (PAH). The current study examined whether perturbations to the TGF-ß/Smad2,3 signalling axis occurred in a monocrotaline (MCT) rodent model of experimental PAH.

Expression of the TGF-ß 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-ß 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-ß receptor (TGFBR) activin-A receptor-like kinase1, TGFBR-2, TGFBR-3 (endoglin), Smad3 and Smad4; as well as TGF-ß signalling and TGF-ß-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-ß/Smad2,3 signalling axis is functionally impaired in monocrotaline-treated rodents with severe pulmonary arterial hypertension, underscoring the potential importance of transforming growth factor-ß/Smad2,3 signalling in the onset or development of pulmonary arterial hypertension.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Q. Lu, B. Patel, E. O. Harrington, and S. Rounds
Transforming growth factor-{beta}1 causes pulmonary microvascular endothelial cell apoptosis via ALK5
Am J Physiol Lung Cell Mol Physiol, May 1, 2009; 296(5): L825 - L838.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
L. Long, A. Crosby, X. Yang, M. Southwood, P. D. Upton, D.-K. Kim, and N. W. Morrell
Altered Bone Morphogenetic Protein and Transforming Growth Factor-{beta} Signaling in Rat Models of Pulmonary Hypertension: Potential for Activin Receptor-Like Kinase-5 Inhibition in Prevention and Progression of Disease
Circulation, February 3, 2009; 119(4): 566 - 576.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
M. Thomas, C. Docx, A. M. Holmes, S. Beach, N. Duggan, K. England, C. Leblanc, C. Lebret, F. Schindler, F. Raza, et al.
Activin-Like Kinase 5 (ALK5) Mediates Abnormal Proliferation of Vascular Smooth Muscle Cells from Patients with Familial Pulmonary Arterial Hypertension and Is Involved in the Progression of Experimental Pulmonary Arterial Hypertension Induced by Monocrotaline
Am. J. Pathol., February 1, 2009; 174(2): 380 - 389.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Sevilla-Perez, M. Konigshoff, G. Kwapiszewska, O. V. Amarie, W. Seeger, N. Weissmann, R. T. Schermuly, R. E. Morty, and O. Eickelberg
Shroom expression is attenuated in pulmonary arterial hypertension
Eur. Respir. J., October 1, 2008; 32(4): 871 - 880.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
Q. Lu
Transforming growth factor-{beta}1 protects against pulmonary artery endothelial cell apoptosis via ALK5
Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L123 - L133.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. L. Zaiman, M. Podowski, S. Medicherla, K. Gordy, F. Xu, L. Zhen, L. A. Shimoda, E. Neptune, L. Higgins, A. Murphy, et al.
Role of the TGF-{beta}/Alk5 Signaling Pathway in Monocrotaline-induced Pulmonary Hypertension
Am. J. Respir. Crit. Care Med., April 15, 2008; 177(8): 896 - 905.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the European Respiratory Society.