help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on February 25, 2005, doi:10.1164/rccm.200404-531OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 11, June 2005, 1279-1285

A more recent version of this article appeared on June 1, 2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200404-531OCv1
171/11/1279    most recent
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 Aono, Y.
Right arrow Articles by Sone, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aono, Y.
Right arrow Articles by Sone, S.

Submitted on April 26, 2004
Accepted on February 16, 2005

Imatinib as a Novel Anti-fibrotic Agent in Bleomycin-induced Pulmonary Fibrosis in Mice

Yoshinori Aono1, Yasuhiko Nishioka1, Mami Inayama1, Momoyo Ugai1, Jun Kishi1, Hisanori Uehara1, Keisuke Izumi1, and Saburo Sone1*

1 Departments of Internal Medicine and Molecular Therapeutics, and Molecular and Environmental Pathology, Course of Medical Oncology, University of Tokushima School of Medicine, Tokushima, Japan

* To whom correspondence should be addressed. E-mail: ssone{at}clin.med.tokushima-u.ac.jp.

Imatinib mesylate is a potent and specific tyrosine kinase inhibitor against c-abl, bcr-abl and c-kit, and has been demonstrated to be highly active in chronic myeloid leukemia and gastrointestinal stromall tumors. Here we examined the anti-fibrotic effects of imatinib using a bleomycin-induced lung fibrosis model in mice because imatinib also inhibits tyrosine kinase of platelet-derived growth factor receptors (PDGFR). Imatinib inhibited the growth of primary murine lung fibroblasts and the autophosphorylation of PDGFR-{beta} induced by PDGF. Administration of imatinib significantly prevented bleomycin-induced pulmonary fibrosis. Analysis of bronchoalveolar lavage cells demonstrated that imatinib did not suppress early inflammation on days 7 and 14 caused by bleomycin, but clearly ameliorated subsequent fibrosis in the late stages. These results suggest that PDGF could be a critical growth factor in the pathogenesis of bleomycin-induced pulmonary fibrosis, and that imatinib might be useful for the treatment of pulmonary fibrosis in humans.
Key words: platelet-derived growth factor, tyrosine kinase, fibroblast




This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
C. Leipner, K. Grun, A. Muller, E. Buchdunger, L. Borsi, H. Kosmehl, A. Berndt, T. Janik, A. Uecker, M. Kiehntopf, et al.
Imatinib mesylate attenuates fibrosis in coxsackievirus b3-induced chronic myocarditis
Cardiovasc Res, July 1, 2008; 79(1): 118 - 126.
[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
 Mol Cancer ResHome page
V. Gioni, T. Karampinas, G. Voutsinas, A. E. Roussidis, S. Papadopoulos, N. K. Karamanos, and D. Kletsas
Imatinib Mesylate Inhibits Proliferation and Exerts an Antifibrotic Effect in Human Breast Stroma Fibroblasts
Mol. Cancer Res., May 1, 2008; 6(5): 706 - 714.
[Abstract] [Full Text] [PDF]

Home page
 Therapeutic Advances in Respiratory DiseaseHome page
P. Rogliani, M. Mura, M. Assunta Porretta, and C. Saltini
Review: New perspectives in the treatment of idiopathic pulmonary fibrosis
Therapeutic Advances in Respiratory Disease, April 1, 2008; 2(2): 75 - 93.
[Abstract] [PDF]

Home page
 JEMHome page
R. Mori, T. J. Shaw, and P. Martin
Molecular mechanisms linking wound inflammation and fibrosis: knockdown of osteopontin leads to rapid repair and reduced scarring
J. Exp. Med., January 21, 2008; 205(1): 43 - 51.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Azuma, Y. Nishioka, Y. Aono, M. Inayama, H. Makino, J. Kishi, M. Shono, K. Kinoshita, H. Uehara, F. Ogushi, et al.
Role of {alpha}1-Acid Glycoprotein in Therapeutic Antifibrotic Effects of Imatinib with Macrolides in Mice
Am. J. Respir. Crit. Care Med., December 15, 2007; 176(12): 1243 - 1250.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
C. J. Scotton and R. C. Chambers
Molecular Targets in Pulmonary Fibrosis: The Myofibroblast in Focus
Chest, October 1, 2007; 132(4): 1311 - 1321.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
N. I. Chaudhary, G. J. Roth, F. Hilberg, J. Muller-Quernheim, A. Prasse, G. Zissel, A. Schnapp, and J. E. Park
Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis
Eur. Respir. J., May 1, 2007; 29(5): 976 - 985.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
R. Vittal, H. Zhang, M. K. Han, B. B. Moore, J. C. Horowitz, and V. J. Thannickal
Effects of the Protein Kinase Inhibitor, Imatinib Mesylate, on Epithelial/Mesenchymal Phenotypes: Implications for Treatment of Fibrotic Diseases
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 35 - 44.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
X. M. Wang, Y. Zhang, H. P. Kim, Z. Zhou, C. A. Feghali-Bostwick, F. Liu, E. Ifedigbo, X. Xu, T. D. Oury, N. Kaminski, et al.
Caveolin-1: a critical regulator of lung fibrosis in idiopathic pulmonary fibrosis
J. Exp. Med., December 25, 2006; 203(13): 2895 - 2906.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
Y. Ishii, S. Fujimoto, and T. Fukuda
Gefitinib Prevents Bleomycin-induced Lung Fibrosis in Mice
Am. J. Respir. Crit. Care Med., September 1, 2006; 174(5): 550 - 556.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. Avivi-Green, M. Singal, and W. F. Vogel
Discoidin Domain Receptor 1-deficient Mice Are Resistant to Bleomycin-induced Lung Fibrosis
Am. J. Respir. Crit. Care Med., August 15, 2006; 174(4): 420 - 427.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
F. J. Martinez and M. P. Keane
Update in diffuse parenchymal lung diseases 2005.
Am. J. Respir. Crit. Care Med., May 15, 2006; 173(10): 1066 - 1071.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Inayama, Y. Nishioka, M. Azuma, S. Muto, Y. Aono, H. Makino, K. Tani, H. Uehara, K. Izumi, A. Itai, et al.
A Novel I{kappa}B Kinase-beta Inhibitor Ameliorates Bleomycin-induced Pulmonary Fibrosis in Mice
Am. J. Respir. Crit. Care Med., May 1, 2006; 173(9): 1016 - 1022.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. I. Chaudhary, A. Schnapp, and J. E. Park
Pharmacologic Differentiation of Inflammation and Fibrosis in the Rat Bleomycin Model
Am. J. Respir. Crit. Care Med., April 1, 2006; 173(7): 769 - 776.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Bonniaud, P. J. Margetts, K. Ask, K. Flanders, J. Gauldie, and M. Kolb
TGF-{beta} and Smad3 Signaling Link Inflammation to Chronic Fibrogenesis
J. Immunol., October 15, 2005; 175(8): 5390 - 5395.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2005 American Thoracic Society 		  ATS State of the Art Course 2008