Wnt signaling plays central roles in embryogenesis/development, skeletal homeostasis, tumour development, and other diseases. The pathway is initiated by Wnt ligands which can be bound and inhibited by sFRP1. Regulation of sFRP1 in lung inflammation needs increased study, and little is known about which cytokines can induce sFRP1, nor the role of gp130 cytokines in its modulation. Here we used AdOSM (Advector expressing mouse Oncostatin M [OSM]) administration to overexpress the gp130 cytokine OSM in mice in vivo, and applied Nanostring, RT-PCR, and immunoblots to measure mRNA and protein levels. OSM induced robust increases in mRNA for sFRP-1 in context of reduced Wnt ligand and receptor mRNA (Wnt10B, Wnt3A, Wnt2, Wnt11, LRP5 and LRP6). Axin-2 mRNA, as a b-catenin target gene, was also suppressed suggesting an inhibition of Wnt signaling pathways. AdOSM could induce sFRP1 in IL-6KO mice, while overexpression of IL-6 (AdIL-6 vector) did not. Immunoblots of total lung extracts showed increases in the 35Kd sFRP1 protein species. In situ hybridization of mouse lung histological sections using specific sFRP1 probes showed staining in the subepithelial layer of the airways, consistent with fibroblast or myofibroblast locations in lung mucosa. In vitro, recombinant OSM stimulated sFRP1 mRNA in cultures of mouse lung fibroblasts and NIH-3T3 cells. The results support the novel observation that OSM can induce sFRP1 in vitro and in vivo, and suggest this axis contributes to the control of Wnt signaling pathways in lung inflammation.
