UBC Theses and Dissertations
Expression of pro-fibrotic factors in the airways of lungs from patients with chronic obstructive pulmonary disease McDonough, John Edward
Chronic obstructive pulmonary disease is characterized by a reduction in lung function caused by a thickening of the bronchiole airway wall and narrowing of its lumen. This remodeling is associated with the development of a peribronchial fibrosis. This study compares the expression of several pro-fibrotic mediators using immunohistochemistry, quantitative RT-PCR, and in situ hybridization to quantitate and localize the expression of these proteins. In lung tissue from patients with GOLD stage 0, 1,3, and 4 COPD the volume fraction of the staining for each mediator in the bronchiolar epithelium of randomly selected airways was measured using image analysis software. The results demonstrated a significant increase in the amount of IL-13, TGF-beta2, PDGF-A, PDGF-Ralpha, and CTGF in the airways of more severe GOLD stage 3 and 4 patients relative to the airways of non-obstructed or mild GOLD 0 and 1 patients. No changes were detected in the expression of TGF-betal, p-SMAD2/3, PDGF-B, or PDGF-Rbeta. Using quantitative RT-PCR and in situ hybridization, the expression and localization of TGFbetal, TGF-beta2, and TGF-beta3 are determined. No differences were found in their level of expression but, in accordance with the immunohistochemical results, high levels of RNA were localized to the bronchiolar epithelium. This study highlights the potential role that the bronchiolar epithelium plays in the development of peribronchial fibrosis and disease pathogenesis in COPD.
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