Journal of Applied Physiology Journal of Applied Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

J Appl Physiol (October 13, 2005). doi:10.1152/japplphysiol.00595.2005
This Article
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
100/2/564    most recent
00595.2005v1
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
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 Google Scholar
Google Scholar
Right arrow Articles by Chen, Y.-F.
Right arrow Articles by Oparil, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, Y.-F.
Right arrow Articles by Oparil, S.
Submitted on May 20, 2005
Accepted on October 7, 2005

Dominant Negative Mutation of the TGF-beta Receptor Blocks Hypoxia-Induced Pulmonary Vascular Remodeling

Yiu-Fai Chen1*, Ji-An Feng1, Peng Li1, Dongqi Xing1, Yun Zhang1, Rosa Serra2, Namasivayam Ambalavanan3, Erum Majid-Hassan1, and Suzanne Oparil1

1 Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
2 Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA
3 Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA

* To whom correspondence should be addressed. E-mail: yfchen{at}uab.edu.

The current study utilized a novel transgenic mouse model that expresses an inducible dominant-negative mutation of the transforming growth factor (TGF)-{beta}type II receptor (DnTGF{beta}RII mouse) to test the hypothesis that TGF-{beta} signaling plays an important role in the pathogenesis of chronic hypoxia-induced increases in pulmonary arterial pressure and vascular and alveolar remodeling. Nine-10 wk old male DnTGF{beta}RII and control nontransgenic (NTG) mice were exposed to normobaric hypoxia (10% O2) or air for 6 wks. Expression of DnTGF{beta}RII was induced by drinking 25 mM ZnSO4 water beginning 1 wk before hypoxic exposure. Hypoxia-induced increases in right ventricular pressure, right ventricular mass, pulmonary arterial remodeling and muscularization were greatly attenuated in DnTGF{beta}RII mice, compared to NTG controls. Further, the stimulatory effects of hypoxic exposure on pulmonary arterial and alveolar collagen content, appearance of {alpha}-smooth muscle actin ({alpha}-SMA) positive cells in alveolar parenchyma, and expression of extracellular matrix molecule (including collagen I and III, periostin and osteopontin) mRNA in whole lung were abrogated in DnTGF{beta}RII mice compared to NTG controls. Hypoxic exposure had no effect on systemic arterial pressure or heart rate in either strain. These data support the hypothesis that endogenous TGF-{beta} plays an important role in pulmonary vascular adaptation to chronic hypoxia and that disruption of TGF-{beta} signaling attenuates hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, pulmonary arterial hypertrophy and muscularization, alveolar remodeling, and expression of extracellular matrix mRNA in whole lung.




This article has been cited by other articles:


Home page
 Circ. Res.Home page
P. Snider, K. N. Standley, J. Wang, M. Azhar, T. Doetschman, and S. J. Conway
Origin of Cardiac Fibroblasts and the Role of Periostin
Circ. Res., November 6, 2009; 105(10): 934 - 947.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. L. Burke, M. G. Frid, C. L. Kunrath, V. Karoor, A. Anwar, B. D. Wagner, D. Strassheim, and K. R. Stenmark
Sustained hypoxia promotes the development of a pulmonary artery-specific chronic inflammatory microenvironment
Am J Physiol Lung Cell Mol Physiol, August 1, 2009; 297(2): L238 - L250.
[Abstract] [Full Text] [PDF]

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
 J. Appl. Physiol.Home page
A. Yndestad, K.-O. Larsen, E. Oie, T. Ueland, C. Smith, B. Halvorsen, I. Sjaastad, O. H. Skjonsberg, T. M. Pedersen, O.-G. Anfinsen, et al.
Elevated levels of activin A in clinical and experimental pulmonary hypertension
J Appl Physiol, April 1, 2009; 106(4): 1356 - 1364.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Ismail, A. Sturrock, P. Wu, B. Cahill, K. Norman, T. Huecksteadt, K. Sanders, T. Kennedy, and J. Hoidal
NOX4 mediates hypoxia-induced proliferation of human pulmonary artery smooth muscle cells: the role of autocrine production of transforming growth factor-{beta}1 and insulin-like growth factor binding protein-3
Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L489 - L499.
[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
 Am. J. Respir. Cell Mol. Bio.Home page
J. S. Guimbellot, J. A. Fortenberry, G. P. Siegal, B. Moore, H. Wen, C. Venglarik, Y.-F. Chen, S. Oparil, E. J. Sorscher, and J. S. Hong
Role of Oxygen Availability in CFTR Expression and Function
Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 514 - 521.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
N. Ambalavanan, T. Nicola, J. Hagood, A. Bulger, R. Serra, J. Murphy-Ullrich, S. Oparil, and Y.-F. Chen
Transforming growth factor-{beta} signaling mediates hypoxia-induced pulmonary arterial remodeling and inhibition of alveolar development in newborn mouse lung
Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L86 - L95.
[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
 Circ. Res.Home page
P. Li, D. Wang, J. Lucas, S. Oparil, D. Xing, X. Cao, L. Novak, M. B. Renfrow, and Y.-F. Chen
Atrial Natriuretic Peptide Inhibits Transforming Growth Factor {beta}-Induced Smad Signaling and Myofibroblast Transformation in Mouse Cardiac Fibroblasts
Circ. Res., February 1, 2008; 102(2): 185 - 192.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Mittal, M. Roth, P. Konig, S. Hofmann, E. Dony, P. Goyal, A.-C. Selbitz, R. T. Schermuly, H. A. Ghofrani, G. Kwapiszewska, et al.
Hypoxia-Dependent Regulation of Nonphagocytic NADPH Oxidase Subunit NOX4 in the Pulmonary Vasculature
Circ. Res., August 3, 2007; 101(3): 258 - 267.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. Zakrzewicz, F. M. Kouri, B. Nejman, G. Kwapiszewska, M. Hecker, R. Sandu, E. Dony, W. Seeger, R. T. Schermuly, O. Eickelberg, et al.
The transforming growth factor-{beta}/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension
Eur. Respir. J., June 1, 2007; 29(6): 1094 - 1104.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
P. Li, S. Oparil, L. Novak, X. Cao, W. Shi, J. Lucas, and Y.-F. Chen
ANP signaling inhibits TGF-beta-induced Smad2 and Smad3 nuclear translocation and extracellular matrix expression in rat pulmonary arterial smooth muscle cells
J Appl Physiol, January 1, 2007; 102(1): 390 - 398.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. L. Wright, H. Tai, R. Wang, X. Wang, and A. Churg
Cigarette smoke upregulates pulmonary vascular matrix metalloproteinases via TNF-{alpha} signaling
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L125 - L133.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
T. E. de Gooyer, K. A. Stevenson, P. Humphries, D. A. C. Simpson, T. A. Gardiner, and A. W. Stitt
Retinopathy Is Reduced during Experimental Diabetes in a Mouse Model of Outer Retinal Degeneration
Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5561 - 5568.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. I. Said
Mediators and modulators of pulmonary arterial hypertension
Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L547 - L558.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
K. R. Stenmark, K. A. Fagan, and M. G. Frid
Hypoxia-Induced Pulmonary Vascular Remodeling: Cellular and Molecular Mechanisms
Circ. Res., September 29, 2006; 99(7): 675 - 691.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1948 by the American Physiological Society.