This Article Full Text Full Text (PDF) All Versions of this Article: 2004-0190OCv1 32/2/99    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kelly, M. M. Articles by Gauldie, J. Search for Related Content PubMed PubMed Citation Articles by Kelly, M. M. Articles by Gauldie, J.

Epithelial Expression of Profibrotic Mediators in a Model of Allergen-Induced Airway Remodeling

Department of Pathology and Molecular Medicine and Centre for Gene Therapeutics, Firestone Institute for Respiratory Health and Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Correspondence and requests for reprints should be addressed to Dr. Jack Gauldie, Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, MDCL-4017, McMaster University, 1200 Main Street West, Hamilton, ON, L8N 3Z5 Canada. E-mail: gauldie{at}mcmaster.ca

Airway remodeling, including subepithelial fibrosis, is a characteristic feature of asthma and likely contributes to the pathogenesis of airway hyperresponsiveness. We examined expression of genes related to airway wall fibrosis in a model of chronic allergen-induced airway dysfunction using laser capture microdissection and quantitative real-time PCR. BALB/c mice were sensitized and subjected to chronic ovalbumin exposure over a 12-wk period, after which they were rested and then harvested 2 and 8 wk after the last exposure. Chronic allergen–exposed mice had significantly increased indices of airway remodeling and airway hyperreactivity at all time points, although no difference in expression of fibrosis-related genes was found when mRNA extracted from whole lung was examined. In contrast, fibrosis-related gene expression was significantly upregulated in mRNA obtained from microdissected bronchial wall at 2 wk after chronic allergen exposure. In addition, when bronchial wall epithelium and smooth muscle were separately microdissected, gene expression of transforming growth factor-ß1 and plasminogen activating inhibitor-1 were significantly upregulated only in the airway epithelium. These data suggest that transforming growth factor-ß1 and other profibrotic mediators produced by airway wall, and specifically, airway epithelium, play an important role in the pathophysiology of airway remodeling.

Key Words: airway hyperresponsiveness • airway remodeling • asthma • laser capture microdissection • transforming growth factor-ß1

This article has been cited by other articles:

				J. F. Alcorn, A. S. Guala, J. van der Velden, B. McElhinney, C. G. Irvin, R. J. Davis, and Y. M. W. Janssen-Heininger Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-{beta}1 J. Cell Sci., April 1, 2008; 121(7): 1036 - 1045. [Abstract] [Full Text] [PDF]

				R. Fattouh, N. G. Midence, K. Arias, J. R. Johnson, T. D. Walker, S. Goncharova, K. P. Souza, R. C. Gregory Jr., S. Lonning, J. Gauldie, et al. Transforming Growth Factor-{beta} Regulates House Dust Mite-induced Allergic Airway Inflammation but Not Airway Remodeling Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 593 - 603. [Abstract] [Full Text] [PDF]

				M. M. Kelly, K. McNagny, D. L. Williams, N. van Rooijen, L. Maxwell, C. Gwozd, C. H. Mody, and P. Kubes The Lung Responds to Zymosan in a Unique Manner Independent of Toll-Like Receptors, Complement, and Dectin-1 Am. J. Respir. Cell Mol. Biol., February 1, 2008; 38(2): 227 - 238. [Abstract] [Full Text] [PDF]

				J. F. Alcorn, L. M. Rinaldi, E. F. Jaffe, M. van Loon, J. H. T. Bates, Y. M. W. Janssen-Heininger, and C. G. Irvin Transforming Growth Factor-beta1 Suppresses Airway Hyperresponsiveness in Allergic Airway Disease Am. J. Respir. Crit. Care Med., November 15, 2007; 176(10): 974 - 982. [Abstract] [Full Text] [PDF]

				H. W. Chu, J. Thaikoottathil, J. G. Rino, G. Zhang, Q. Wu, T. Moss, Y. Refaeli, R. Bowler, S. E. Wenzel, Z. Chen, et al. Function and Regulation of SPLUNC1 Protein in Mycoplasma Infection and Allergic Inflammation J. Immunol., September 15, 2007; 179(6): 3995 - 4002. [Abstract] [Full Text] [PDF]

				J. R. Johnson, F. K. Swirski, B. U. Gajewska, R. E. Wiley, R. Fattouh, S. R. Pacitto, J. K. Wong, M. R. Stampfli, and M. Jordana Divergent immune responses to house dust mite lead to distinct structural-functional phenotypes Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L730 - L739. [Abstract] [Full Text] [PDF]

				C. M. Lloyd and D. S. Robinson Allergen-induced airway remodelling Eur. Respir. J., May 1, 2007; 29(5): 1020 - 1032. [Abstract] [Full Text] [PDF]

				E. D. Fixman, A. Stewart, and J. G. Martin Basic mechanisms of development of airway structural changes in asthma Eur. Respir. J., February 1, 2007; 29(2): 379 - 389. [Abstract] [Full Text] [PDF]

				K. Shinagawa, J. A. Martin, V. A. Ploplis, and F. J. Castellino Coagulation Factor Xa Modulates Airway Remodeling in a Murine Model of Asthma Am. J. Respir. Crit. Care Med., January 15, 2007; 175(2): 136 - 143. [Abstract] [Full Text] [PDF]

				A. Churg, H. Tai, T. Coulthard, R. Wang, and J. L. Wright Cigarette Smoke Drives Small Airway Remodeling by Induction of Growth Factors in the Airway Wall Am. J. Respir. Crit. Care Med., December 15, 2006; 174(12): 1327 - 1334. [Abstract] [Full Text] [PDF]

				E. K. Chu, J. Cheng, J. S. Foley, B. H. Mecham, C. A. Owen, K. J. Haley, T. J. Mariani, I. S. Kohane, D. J. Tschumperlin, and J. M. Drazen Induction of the Plasminogen Activator System by Mechanical Stimulation of Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., December 1, 2006; 35(6): 628 - 638. [Abstract] [Full Text] [PDF]

				S. Y. Leung, A. Niimi, A. Noble, T. Oates, A. S. Williams, S. Medicherla, A. A. Protter, and K. F. Chung Effect of Transforming Growth Factor-beta Receptor I Kinase Inhibitor 2,4-Disubstituted Pteridine (SD-208) in Chronic Allergic Airway Inflammation and Remodeling J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 586 - 594. [Abstract] [Full Text] [PDF]

				M. M. Choe, P. H. S. Sporn, and M. A. Swartz Extracellular Matrix Remodeling by Dynamic Strain in a Three-Dimensional Tissue-Engineered Human Airway Wall Model Am. J. Respir. Cell Mol. Biol., September 1, 2006; 35(3): 306 - 313. [Abstract] [Full Text] [PDF]

				M. M. Kelly, R. Leigh, S. E. Gilpin, E. Cheng, G. E. M. Martin, K. Radford, G. Cox, and J. Gauldie Cell-specific Gene Expression in Patients with Usual Interstitial Pneumonia Am. J. Respir. Crit. Care Med., September 1, 2006; 174(5): 557 - 565. [Abstract] [Full Text] [PDF]

				A. S. Augustus, J. Buchanan, T.-S. Park, K. Hirata, H.-l. Noh, J. Sun, S. Homma, J. D'armiento, E. D. Abel, and I. J. Goldberg Loss of Lipoprotein Lipase-derived Fatty Acids Leads to Increased Cardiac Glucose Metabolism and Heart Dysfunction J. Biol. Chem., March 31, 2006; 281(13): 8716 - 8723. [Abstract] [Full Text] [PDF]

				D. H. Broide, T. Lawrence, T. Doherty, J. Y. Cho, M. Miller, K. McElwain, S. McElwain, and M. Karin Allergen-induced peribronchial fibrosis and mucus production mediated by I{kappa}B kinase {beta}-dependent genes in airway epithelium PNAS, December 6, 2005; 102(49): 17723 - 17728. [Abstract] [Full Text] [PDF]

				H. W. Chu, J. G. Rino, R. B. Wexler, K. Campbell, R. J. Harbeck, and R. J. Martin Mycoplasma pneumoniae infection increases airway collagen deposition in a murine model of allergic airway inflammation Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L125 - L133. [Abstract] [Full Text] [PDF]

				E. K. Chu and J. M. Drazen Asthma: One Hundred Years of Treatment and Onward Am. J. Respir. Crit. Care Med., June 1, 2005; 171(11): 1202 - 1208. [Abstract] [Full Text] [PDF]