Glycogen synthase kinase 3β and β-catenin are involved in the injury and repair of bronchial epithelial cells induced by scratching

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 3β (GSK3β) inhibited the wound closure, whereas over-expression of β-catenin promoted it. We also demonstrated that scratching caused the inhibitory phosphorylation of GSK3β probably through the PKC signaling pathway, and resulted in β-catenin accumulation which was abolished by the GSK3β over-expression or GF109203X, a PKC inhibitor. Moreover, our results showed that scratching induced nuclear translocation of β-catenin and thereby activated β-catenin/Tcf signaling, whereas the transcription activation could also be prevented by the GSK3β over-expression. Finally, we found that the accumulation of β-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 GSK3β activity which can lead to activation of the downstream signaling through β-catenin, providing a possible mechanism implicated in the injury and repair of airway epithelium.