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Published ahead of print on May 25, 2006, doi:10.1164/rccm.200510-1648OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 5, September 2006, 557-565

A more recent version of this article appeared on September 1, 2006
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Submitted on October 21, 2005
Accepted on May 25, 2006

Cell Specific Gene Expression in Patients with Usual Interstitial Pneumonia

Margaret M Kelly1, Richard Leigh2, Sarah E Gilpin1, Elaine Cheng1, Gail E.M. Martin1, Katherine Radford2, Gerard Cox2, and Jack Gauldie1*

1 Department of Pathology and Molecular Medicine, Centre for Gene Therapeutics, McMaster University, Hamilton, Ontario, Canada, 2 Firestone Institute for Respiratory Health and Department of Medicine, McMaster University, St. Joseph's Healthcare, Hamilton, Ontario, Canada

* To whom correspondence should be addressed. E-mail: gauldie{at}mcmaster.ca.

Rationale: Usual interstitial pneumonia is characterized by extracellular matrix deposition and the development of pulmonary fibrosis. Fibroblastic foci found in the lung are believed to represent an early stage in the evolution of this disease. Objectives: To compare gene expression profiles in different components of lung tissue (fibroblastic foci, adjacent epithelium, and areas of type II pneumocyte hyperplasia) from patients with usual interstitial pneumonia, and contrast these profiles to distal, uninvolved (control) alveolar tissue from patients undergoing lung resection for cancer. Methods: Lung resection tissue (usual interstitial pneumonia, n = 11; controls, n = 11), was snap-frozen for subsequent laser capture microdissection, followed by mRNA extraction, linear amplification and quantitative real-time PCR. Results: In patients with usual interstitial pneumonia, tissue inhibitor of matrix metalloprotease-1 and matrix metalloprotease-2 gene expression was upregulated within the fibroblastic foci compared to the overlying epithelium (p = 0.03, p = 0.02), and to control alveoli (p = 0.001, p = 0.04), respectively. Matrix metalloprotease-9, and -7 as well as osteopontin were upregulated in fibroblastic foci (p = 0.01, p = 0.08, p = 0.08), the adjacent epithelium (p = 0.001, p = 0.001, p = 0.03), and the hyperplastic type II pneumocytes (p = 0.02, p = 0.001, p = 0.08) respectively, compared to control alveoli. Conclusion: Altered gene expression of important profibrotic mediators in the different cellular lung compartments in patients with usual interstitial pneumonia likely plays an important role in pathogenesis of the deranged extracellular matrix deposition and subsequent fibrosis in this condition.
Key words: Pulmonary Fibrosis, tissue inhibitor of matrix metalloprotease-1, Matrix metalloprotease, Microdissection.




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