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Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis.
Eur. Respir. J. 37, 79-87 (2011)
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with unknown pathogenesis. The WNT/β-catenin pathway has recently been reported to be operative in epithelial cells in IPF. Dickkopf (DKK) proteins are known to regulate WNT signalling via interaction with Kremen (KRM) receptors, yet their expression and role in the adult lung and in IPF has not been addressed. We analysed the expression, localisation and function of DKK and KRM proteins in IPF lungs using Western blotting, quantitative RT-PCR, immunohistochemistry, ELISA and functional in vitro studies. Enhanced expression of DKK1 and DKK4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localised in basal bronchial epithelial cells. Furthermore, prominent expression of all proteins was observed in hyperplastic alveolar epithelial cells in IPF. Quantitative measurement of DKK1 revealed enhanced protein expression in the bronchoalveolar lumen of IPF patients. Finally, functional studies using human bronchial and alveolar epithelial cell lines demonstrated that WNT-induced epithelial cell proliferation is regulated by DKK1 in a dose-dependent fashion. In summary, DKK proteins are expressed in the lung epithelium in IPF. DKK proteins influence epithelial cell proliferation and may, therefore, be suitable therapeutic targets for IPF.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Dickkopf proteins; lung epithelial cells; pulmonary fibrosis; WNT signalling
Language
english
Publication Year
2011
Prepublished in Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
0903-1936
e-ISSN
1399-3003
Journal
European Respiratory Journal
Quellenangaben
Volume: 37,
Issue: 1,
Pages: 79-87
Publisher
European Respiratory Society
Publishing Place
Sheffield
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Research field(s)
Lung Research
PSP Element(s)
G-551800-001
Erfassungsdatum
2010-12-31