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Title: | Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF-1, FGF-2, and FGFR-1 | Authors: | Kranenburg, A.R. WIDYASTUTI, Anna Mooi, W.J. Saxena, P.R. Sterk, P.J. de Boer, W.I. Sharma, H.S. |
Issue Date: | 2005 | Publisher: | WILEY | Source: | Journal of Pathology, 206 (1) , p. 28 -38 | Abstract: | An important feature of chronic obstructive pulmonary disease (COPD) is airway remodelling, the molecular mechanisms of which are poorly understood. In this study, the role of fibroblast growth factors (FGF-1 and FGF-2) and their receptor, FGFR-1, was assessed in bronchial airway wall remodelling in patients with COPD (FEV1 < 75%; n = 15) and without COPD (FEV1 > 85%; n = 16). FGF-1 and FGFR-1 were immunolocalized in bronchial epithelium, airway smooth muscle (ASM), submucosal glandular epithelium, and vascular smooth muscle. Quantitative digital image analysis revealed increased cytoplasmic expression of FGF-2 in bronchial epithelium (0.35 +/- 0.03 vs 0.20 +/- 0.04, p < 0.008) and nuclear localization in ASM (p < 0.0001) in COPD patients compared with controls. Elevated levels of FGFR-1 in ASM (p < 0.005) and of FGF-1 (p < 0.04) and FGFR-I (P < 0.001) in bronchial epithelium were observed. In cultured human ASM cells, FGF-1 and/or FGF-2 (10 ng/ml) induced cellular proliferation, as shown by [H-3]thymidine incorporation and by cell number counts. Steady-state mRNA levels of FGFR-1 were elevated in human ASM cells treated with either FGF-1 or FGF-2. The increased bronchial expression of fibroblast growth factors and their receptor in patients with COPD, and the mitogenic response of human ASM cells to FGFs in vitro suggest a potential role for the FGF/FGFR-1 system in the remodelling of bronchial airways in COPD. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. | Keywords: | chronic obstructive pulmonary disease;fibroblast growth factor;airway remodelling;airway smooth muscle;gene expression;human | Document URI: | http://hdl.handle.net/1942/30743 | Link to publication/dataset: | http://www.scopus.com/inward/record.url?eid=2-s2.0-18144406878&partnerID=MN8TOARS | ISSN: | 0022-3417 | e-ISSN: | 1096-9896 | DOI: | 10.1002/path.1748 | ISI #: | WOS:000228732600004 | Rights: | 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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