Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps.

Wnt Signaling in Chronic Rhinosinusitis with Nasal Polyps.

Am J Respir Cell Mol Biol. 2017 Jan 06;:

Authors: Böscke R, Vladar EK, Könnecke M, Hüsing B, Linke R, Pries R, Reiling N, Axelrod JD, Nayak JV, Wollenberg B

Abstract
The signaling pathways that sustain the disease process of chronic rhinosinusitis with nasal polyps (CRSwNP) remain poorly understood. We sought to determine the expression levels of Wnt signaling genes in CRSwNP, and to study the role of the Wnt pathway in inflammation and epithelial remodeling in the nasal mucosa. Microarrays and RT-qPCR comparing gene expression in matched nasal polyps (NP) and inferior turbinates (IT) revealed that WNT2B, WNT3A, WNT4, WNT7A, WNT7B and FZD2 were upregulated, and FZD1, LRP5, LRP6 and WIF1 downregulated in NPs. Immunolabeling showed robust expression of Wnt ligands, nuclear beta-catenin and AXIN2 in NP tissue, suggesting that Wnt/beta-catenin signaling is activated in NPs. We used primary human nasal epithelial cell (HNEpC) cultures to test the functional consequences of Wnt pathway activation. Monolayer HNEpCs treated with recombinant human WNT3A (rhWNT3A), but not rhWNT4 had altered epithelial morphology and decreased adhesion without loss of viability. We found that neither rhWNT3A nor rhWNT4 treatment induced proliferation. The expression and release of inflammatory cytokines IL-6 and GM-CSF were increased after rhWNT3A exposure of HNEpCs. When differentiated at an air-liquid interface, rhWNT3A- and WNT agonist, but not rhWNT4-treated HNEpCs had abnormal epithelial architecture, failed to undergo motile ciliogenesis, and had defective non-canonical Wnt (planar cell polarity) signaling. Based on these results, we propose a model in which Wnt/beta-catenin signaling sustains mucosal inflammation and leads to a spectrum of changes consistent with those seen during epithelial remodeling in NPs.

PMID: 28059551 [PubMed - as supplied by publisher]

from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2jmCvDg
via IFTTT