PT  - JOURNAL ARTICLE
AU  - E-M. Pfaff
AU  - S. Becker
AU  - A. Günther
AU  - M. Königshoff
TI  - Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis
AID  - 10.1183/09031936.00142409
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj01424-2009
4099  - http://erj.ersjournals.com/content/early/2010/07/22/09031936.00142409.short
4100  - http://erj.ersjournals.com/content/early/2010/07/22/09031936.00142409.full
AB  - 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 signaling 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, localization, 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 4 and KRM1 was detected in lung homogenates of IPF patients compared with transplant donors. Immunohistochemistry revealed that DKK1 was predominantly localized 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 sum, 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.