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Cell-specific Gene Expression in Patients with Usual Interstitial Pneumonia

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

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

Rationale: Usual interstitial pneumonia (UIP) 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 2 pneumocyte hyperplasia) from patients with UIP, and contrast these profiles to distal, uninvolved (control) alveolar tissue from patients undergoing lung resection for cancer.

Methods: Lung resection tissue (UIP, n = 11; controls, n = 11) was snap-frozen for subsequent laser capture microdissection, followed by mRNA extraction, linear amplification, and quantitative real-time polymerase chain reaction.

Results: In patients with UIP, tissue inhibitor of matrix metalloprotease-1 and matrix metalloprotease (MMP)-2 gene expression was up-regulated within the fibroblastic foci compared with the overlying epithelium (p = 0.03, p = 0.02), and to control alveoli (p = 0.001, p = 0.04), respectively. MMP-9 and MMP-7, as well as osteopontin, were up-regulated 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 2 pneumocytes (p = 0.02, p = 0.001, p = 0.08), respectively, compared with control alveoli.

Conclusion: Altered gene expression of important profibrotic mediators in the different cellular lung compartments in patients with UIP likely plays an important role in pathogenesis of the deranged extracellular matrix deposition and subsequent fibrosis in this condition.

Key Words: lung diseases, interstitial • matrix metalloprotease • microdissection • pulmonary fibrosis • tissue inhibitor of matrix metalloprotease-1

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