Objectives: To understand the link between CF airway remodeling and planar cell polarity (PCP), an intracellular protein network controlling the orientation of epithelial cells in the plane of the tissue, ciliogenesis and cilia motion. Methods: Expression of genes encoding components of PCP network, in particular the core protein CELSR3, and their regulation by TGBβ were studied in vivo and in mouse nasal epithelial cells in 3-D primary cultures (MNEC) from F508del-CF and Scnn1b-tg/+ (βENaC-overexpressing; Tg/+) mice. Results: In naïve conditions, no difference in PCP gene expression was found between CF and wild-type mouse lungs or MNECs. In bleomycininduced lung remodeling (Huaux, Noel et al, PLoS One 2013), CELSR3 expression was more markedly decreased in CF than in wild-type cells. The effect correlated with levels of inflammatory and fibrosis markers (IL-6, TGFβ, collagen contents and TIMP-1). In Tg/+-MNECs, expression of CELSR3 and other PCP genes was significantly deregulated in comparison with wild-type cells. Cell exposure to TGFβ (15ng/ml, 6 days) decreased the expression of CELSR3 and induced epithelial to mesenchymal transition, characterized by down-regulation of epithelial markers (zonula occludens- 1) and upregulation of mesenchymal markers (α-smooth muscle actin, fibronectin and vimentin). In Tg/+ cells, the effect was more marked and not fully reversed by the TGFβ-receptor type I and II inhibitor GW-788388. The inhibitor alone promoted apicobasal polarity and mucociliary differentiation (increased transepithelial electrical resistance and expression of epithelial markers, and decreased expression of mesenchymal markers) in both MNEC genotypes, with more pronounced effects in Tg/+ cells. Conclusion: Our data support the view that PCP is deregulated in airways of CF mouse models and contributes to the pulmonary phenotype. Intrinsic and extrinsic factors impair PCP signaling, rendering CF airway epithelial cells more susceptible to tissue remodeling.