Dickkopf proteins influence lung epithelial cell proliferation in idiopathic pulmonary fibrosis

Rationale: 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. Methods: We analyzed 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. Results: Enhanc…