Premium
Chronic obstructive pulmonary disease is associated with enhanced bronchial expression of FGF‐1, FGF‐2, and FGFR‐1
Author(s) -
Kranenburg Andor R,
WillemsWidyastuti Anna,
Mooi Wolter J,
Saxena Pramod R,
Sterk Peter J,
de Boer Willem I,
Sharma Hari S
Publication year - 2005
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1748
Subject(s) - fibroblast growth factor , copd , fibroblast , fibroblast growth factor receptor , epithelium , medicine , respiratory epithelium , endocrinology , receptor , pathology , biology , in vitro , biochemistry
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 (FEV 1 < 75%; n = 15) and without COPD (FEV 1 > 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‐1 ( 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 [ 3 H]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 © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.