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


     

J Appl Physiol (February 24, 2005). doi:10.1152/japplphysiol.01360.2004
This Article
Right arrow Full Text (PDF) Free
Right arrow All Versions of this Article:
99/1/298    most recent
01360.2004v1
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 Nethery, D. E.
Right arrow Articles by Kern, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nethery, D. E.
Right arrow Articles by Kern, J. A.
Submitted on December 7, 2004
Accepted on February 19, 2005

Expression of Mutant Human Epidermal Receptor 3 Attenuates Lung Fibrosis and Improves Survival in Mice

David E. Nethery1, Bethany B. Moore2, George Minowada1, James Carroll3, Jihane A. Faress1, and Jeffrey A. Kern1*

1 Department of Internal Medicine, Pulmonary and Critical Care Division, University Hospitals, Case Western Reserve University, Cleveland, OH, USA
2 Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Michigan Medical School, Ann Arbor, MI, USA
3 Department of Internal Medicine, Pulmonary and Critical Care Division, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA

* To whom correspondence should be addressed. E-mail: jeffrey.kern{at}uhhs.com.

Neuregulin-1 (NRG-1), binding to the human epidermal growth factor receptor HER2/HER3, plays a role in pulmonary epithelial cell proliferation and recovery from injury in vitro. We hypothesized that activation of HER2/HER3 by NRG-1 would also play a role in recovery from in vivo lung injury. We tested this hypothesis using bleomycin lung injury of transgenic mice incapable of signaling through HER2/HER3 due to lung-specific dominant negative HER3 (DNHER3) expression. In animals expressing DNHER3, protein leak, cell infiltration and NRG- 1 levels in bronchoalveolar lavage fluid (BALF) increased after injury similar to non-transgenic littermate control animals. However, HER2/HER3 was not activated and DNHER3 animals displayed fewer lung morphologic changes at 10 and 21 days after injury (p<0.01). In addition, they contained 51% less collagen in injured lungs (p<0.05). TGF{beta}-1 did not increase in BALF from DNHER3 mice compared to non-transgenic littermate mice (p<0.05), suggesting a mechanism for the decreased fibrosis was lack of TGF{beta}-1 induction in DNHER3 mice. Severe lung injury (0.08 units bleomycin) resulted in 80% mortality of non-transgenic mice, but only 35% mortality in DNHER3 transgenic mice (p=0.04). Thus, inhibition of HER2/HER3 signaling protects against pulmonary fibrosis and improves survival.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. D. Hardie, C. Davidson, M. Ikegami, G. D. Leikauf, T. D. Le Cras, A. Prestridge, J. A. Whitsett, and T. R. Korfhagen
EGF receptor tyrosine kinase inhibitors diminish transforming growth factor-{alpha}-induced pulmonary fibrosis
Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1217 - L1225.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
E. Purevdorj, K. Zscheppang, H. G. Hoymann, A. Braun, D. von Mayersbach, M.-J. Brinkhaus, A. Schmiedl, and C. E. L. Dammann
ErbB4 deletion leads to changes in lung function and structure similar to bronchopulmonary dysplasia
Am J Physiol Lung Cell Mol Physiol, March 1, 2008; 294(3): L516 - L522.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. A. Faress, D. E. Nethery, E. F. O. Kern, R. Eisenberg, F. J. Jacono, C. L. Allen, and J. A. Kern
Bleomycin-induced pulmonary fibrosis is attenuated by a monoclonal antibody targeting HER2
J Appl Physiol, December 1, 2007; 103(6): 2077 - 2083.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. E. Nethery, S. Ghosh, S. C. Erzurum, and J. A. Kern
Inactivation of neuregulin-1 by nitration
Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L287 - L293.
[Abstract] [Full Text] [PDF]


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