cyclin-d1 and Pruritus

The ability of airway epithelium to repair itself is an important step in the resolution of airway inflammation and diseases. To explore the cellular and molecular events involved in it, we established an in vitro injury and repair model by scratching a monolayer of bronchial epithelial cells (BECs) and found that the closure of scratch-wounded gaps in BECs required cell migration and proliferation. Our studies further proved that over-expression of glycogen synthase kinase 3beta (GSK3beta) inhibited the wound closure, whereas over-expression of beta-catenin promoted it. We also demonstrated that scratching caused the inhibitory phosphorylation of GSK3beta probably through the PKC signaling pathway, and resulted in beta-catenin accumulation which was abolished by the GSK3beta over-expression or GF109203X, a PKC inhibitor. Moreover, our results showed that scratching induced nuclear translocation of beta-catenin and thereby activated beta-catenin/Tcf signaling, whereas the transcription activation could also be prevented by the GSK3beta over-expression. Finally, we found that the accumulation of beta-catenin was involved in the repair of scratch wounds by promoting the expression of cyclin D1 that linked to cell proliferation. Taken together, our studies suggest that the scratching-induced injury and repair of BECs may involve inhibition of GSK3beta activity which can lead to activation of the downstream signaling through beta-catenin, providing a possible mechanism implicated in the injury and repair of airway epithelium.

Topics: Active Transport, Cell Nucleus; Animals; beta Catenin; Bronchi; Cell Movement; Cell Proliferation; Cell Shape; Cells, Cultured; Cyclin D1; Epithelial Cells; Gene Expression Regulation, Enzymologic; Glycogen Synthase Kinase 3; Indoles; Maleimides; Mutation; Phosphorylation; Protein Kinase C; Pruritus; Signal Transduction; Swine; TCF Transcription Factors