help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hocher, B.
Right arrow Articles by Theuring, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hocher, B.
Right arrow Articles by Theuring, F.

Am. J. Respir. Cell Mol. Biol., Volume 23, Number 1, July, 2000 19-26

Pulmonary Fibrosis and Chronic Lung Inflammation in ET-1 Transgenic Mice

Berthold Hocher, Anja Schwarz, Karen A. Fagan, Christa Thöne-Reineke, Karim El-Hag, Heike Kusserow, Saban Elitok, Christian Bauer, Hans-H. Neumayer, David M. Rodman, and Franz Theuring

Department of Nephrology and Institute of Pharmacology and Toxicology, University Hospital Charité, Humboldt University of Berlin; Institute of Molecular Biology and Biochemistry, Free University of Berlin, Berlin, Germany; and Cardiovascular Pulmonary Research Laboratory and Division of Pulmonary Sciences and Critical Care Medicine, University Hospital, Denver, Colorado

The pulmonary endothelin (ET) system has been implicated in the pathogenesis of chronic lung diseases such as pulmonary hypertension, asthma, chronic obstructive lung disease, idiopathic pulmonary fibrosis, and bronchiolitis obliterans. However, the etiologic role of ET-1 in these diseases has not yet been established. We recently demonstrated that ET-1 transgenic mice, generated using the human prepro-ET-1 expression cassette including the cis-acting transcriptional regulatory elements, had predominant transgene expression in lung, brain, and kidney. We used these mice in the present study to analyze the pathophysiologic consequences of long-term pulmonary overexpression of ET-1. We found that ET-1 overexpression in the lungs did not result in significant pulmonary hypertension, but did result in development of a progressive pulmonary fibrosis and recruitment of inflammatory cells (predominantly CD4-positive cells). Our study provides evidence that a long-term activated pulmonary ET system, without any other stimuli, produces chronic lymphocytic inflammation and lung fibrosis. This suggests that overexpression of ET-1 may be a central event in the pathogenesis of lung diseases associated with fibrosis and chronic inflammation, such as pulmonary fibrosis and bronchiolitis.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
P. Kulasekaran, C. A. Scavone, D. S. Rogers, D. A. Arenberg, V. J. Thannickal, and J. C. Horowitz
Endothelin-1 and Transforming Growth Factor-{beta}1 Independently Induce Fibroblast Resistance to Apoptosis via AKT Activation
Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 484 - 493.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
A. Tyndall, M. Matucci-Cerinic, and U. Muller-Ladner
Future targets in the management of systemic sclerosis
Rheumatology, June 1, 2009; 48(suppl_3): iii49 - iii53.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
D. Abraham
Role of endothelin in lung fibrosis
Eur. Respir. Rev., December 1, 2008; 17(109): 145 - 150.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Iglarz, C. Binkert, K. Morrison, W. Fischli, J. Gatfield, A. Treiber, T. Weller, M. H. Bolli, C. Boss, S. Buchmann, et al.
Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist
J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 736 - 745.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
R. M. Silver
Endothelin and scleroderma lung disease
Rheumatology, October 1, 2008; 47(suppl_5): v25 - v26.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A U Wells, N Hirani, and on behalf of the BTS Interstitial Lung Disease Gui
Interstitial lung disease guideline
Thorax, September 1, 2008; 63(Suppl_5): v1 - v58.
[Full Text] [PDF]

Home page
 Eur Heart JHome page
C. F. Opitz, R. Ewert, W. Kirch, and D. Pittrow
Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?
Eur. Heart J., August 2, 2008; 29(16): 1936 - 1948.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Behr and J. H. Ryu
Pulmonary hypertension in interstitial lung disease
Eur. Respir. J., June 1, 2008; 31(6): 1357 - 1367.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
V. Seyrantepe, A. Hinek, J. Peng, M. Fedjaev, S. Ernest, Y. Kadota, M. Canuel, K. Itoh, C. R. Morales, J. Lavoie, et al.
Enzymatic Activity of Lysosomal Carboxypeptidase (Cathepsin) A Is Required for Proper Elastic Fiber Formation and Inactivation of Endothelin-1
Circulation, April 15, 2008; 117(15): 1973 - 1981.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
J. Dupuis and M. M. Hoeper
Endothelin receptor antagonists in pulmonary arterial hypertension
Eur. Respir. J., February 1, 2008; 31(2): 407 - 415.
[Abstract] [Full Text] [PDF]

Home page
 ERRHome page
R. M. du Bois
Blocking endothelin: breaking new ground
Eur. Respir. Rev., August 1, 2007; 16(102): 24 - 29.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. K. Kim and H. A. Chapman
Endothelin-1 as Initiator of Epithelial-Mesenchymal Transition: Potential New Role for Endothelin-1 during Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 1 - 2.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. Jain, P. W. Shaul, Z. Borok, and B. C. Willis
Endothelin-1 Induces Alveolar Epithelial-Mesenchymal Transition through Endothelin Type A Receptor-Mediated Production of TGF-beta1
Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 38 - 47.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
M. Oka, V. Karoor, N. Homma, T. Nagaoka, E. Sakao, S. M. Golembeski, J. Limbird, M. Imamura, S. A. Gebb, K. A. Fagan, et al.
Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension
Cardiovasc Res, June 1, 2007; 74(3): 377 - 387.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. Gunther, B. Enke, P. Markart, P. Hammerl, H. Morr, J. Behr, G. Stahler, W. Seeger, F. Grimminger, I. Leconte, et al.
Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open label study
Eur. Respir. J., April 1, 2007; 29(4): 713 - 719.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
T. Quaschning, F. Voss, K. Relle, P. Kalk, N. Vignon-Zellweger, T. Pfab, C. Bauer, F. Theilig, S. Bachmann, A. Kraemer-Guth, et al.
Lack of Endothelial Nitric Oxide Synthase Promotes Endothelin-Induced Hypertension: Lessons from Endothelin-1 Transgenic/Endothelial Nitric Oxide Synthase Knockout Mice
J. Am. Soc. Nephrol., March 1, 2007; 18(3): 730 - 740.
[Abstract] [Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
J. H. Ryu, M. J. Krowka, K. L. Swanson, P. A. Pellikka, and M. D. McGoon
Pulmonary Hypertension in Patients With Interstitial Lung Diseases
Mayo Clin. Proc., March 1, 2007; 82(3): 342 - 350.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Y. Sanders, P. Kumbla, and J. S. Hagood
Enhanced Myofibroblastic Differentiation and Survival in Thy-1(-) Lung Fibroblasts
Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 226 - 235.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
M. Sticherling
The role of endothelin in connective tissue diseases
Rheumatology, October 1, 2006; 45(suppl_3): iii8 - iii10.
[Abstract] [Full Text] [PDF]

Home page
 Rheumatology (Oxford)Home page
V. Kolb-Bachofen, A. Kuhn, and C. V. Suschek
The role of nitric oxide
Rheumatology, October 1, 2006; 45(suppl_3): iii17 - iii19.
[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 page
 Exp. Biol. Med.Home page
J. R. Wahl, N. J. Goetsch, H. J. Young, R. J. Van Maanen, J. D. Johnson, A. S. Pea, and A. Brittingham
Murine Macrophages Produce Endothelin-1 After Microbial Stimulation
Experimental Biology and Medicine, October 1, 2005; 230(9): 652 - 658.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
F. Chua, J. Gauldie, and G. J. Laurent
Pulmonary Fibrosis: Searching for Model Answers
Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 9 - 13.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
C. L. Afonso, G. Delhon, E. R. Tulman, Z. Lu, A. Zsak, V. M. Becerra, L. Zsak, G. F. Kutish, and D. L. Rock
Genome of Deerpox Virus
J. Virol., January 15, 2005; 79(2): 966 - 977.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
J. M. Williams, J. S. Pollock, and D. M. Pollock
Arterial Pressure Response to the Antioxidant Tempol and ETB Receptor Blockade in Rats on a High-Salt Diet
Hypertension, November 1, 2004; 44(5): 770 - 775.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
N R Simler, P E Brenchley, A W Horrocks, S M Greaves, P S Hasleton, and J J Egan
Angiogenic cytokines in patients with idiopathic interstitial pneumonia
Thorax, July 1, 2004; 59(7): 581 - 585.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
T. G von Lueder, H. Kjekshus, T. Edvardsen, E. Oie, S. Urheim, L. E. Vinge, M. S. Ahmed, O. A Smiseth, and H. Attramadal
Mechanisms of elevated plasma endothelin-1 in CHF: congestion increases pulmonary synthesis and secretion of endothelin-1
Cardiovasc Res, July 1, 2004; 63(1): 41 - 50.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
L. L. Yang, R. Gros, M. G. Kabir, A. Sadi, A. I. Gotlieb, M. Husain, and D. J. Stewart
Conditional Cardiac Overexpression of Endothelin-1 Induces Inflammation and Dilated Cardiomyopathy in Mice
Circulation, January 20, 2004; 109(2): 255 - 261.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
T. Carpenter, S. Schomberg, W. Steudel, J. Ozimek, K. Colvin, K. Stenmark, and D. D. Ivy
Endothelin B Receptor Deficiency Predisposes to Pulmonary Edema Formation via Increased Lung Vascular Endothelial Cell Growth Factor Expression
Circ. Res., September 5, 2003; 93(5): 456 - 463.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
M. W. Epperly, H. Guo, J. E. Gretton, and J. S. Greenberger
Bone Marrow Origin of Myofibroblasts in Irradiation Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., August 1, 2003; 29(2): 213 - 224.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
T. Quaschning, S. Kocak, C. Bauer, H.-H. Neumayer, J. Galle, and B. Hocher
Increase in nitric oxide bioavailability improves endothelial function in endothelin-1 transgenic mice
Nephrol. Dial. Transplant., March 1, 2003; 18(3): 479 - 483.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
S. Dauger, L. Ferkdadji, G. Saumon, G. Vardon, M. Peuchmaur, C. Gaultier, and J. Gallego
Neonatal Exposure to 65% Oxygen Durably Impairs Lung Architecture and Breathing Pattern in Adult Mice
Chest, February 1, 2003; 123(2): 530 - 538.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Fujita, R. J. Mason, C. Cool, J. M. Shannon, N. Hara, and K. A. Fagan
Pulmonary hypertension in TNF-alpha -overexpressing mice is associated with decreased VEGF gene expression
J Appl Physiol, December 1, 2002; 93(6): 2162 - 2170.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. A. Fagan
Physiological and Genomic Consequences of Intermittent Hypoxia: Selected Contribution: Pulmonary hypertension in mice following intermittent hypoxia
J Appl Physiol, June 1, 2001; 90(6): 2502 - 2507.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2000 American Thoracic Society. 		  Red In Translatin