c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-{gamma}1 transcription

c-Jun is an activating protein 1 (AP-1) transcription factor and implicated in many aspects of cellular functions, but its exact role in the regulation of early intestinal epithelial restitution after injury remains largely unknown. Phospholipase C-1 (PLC1) catalyzes hydrolysis of phosphatidylinositol 4,5 biphosphate into the second messenger diacylglycerol and inositol 1,4,5 triphosphate, coordinates Ca2+ store mobilization, and regulates cell migration and proliferation in response to stress. Here we reported that c-Jun upregulates PLC1 expression and enhances PLC1-induced Ca2+ signaling, thus promoting intestinal epithelial restitution after wounding. Ectopically expressed c-Jun increased PLC1 expression at the transcription level, and this stimulation is mediated by directly interacting with AP-1 and CCAAT-enhancer-binding protein (C/EBP) binding sites that are located at the proximal region of the rat PLC1 promoter. Increased levels of PLC1 by c-Jun elevated cytosolic free Ca2+ concentration and stimulated intestinal epithelial cell migration over the denuded area after wounding. The c-Jun-mediated PLC1/Ca2+ signal also plays an important role in polyamine-induced cell migration after wounding because increased c-Jun rescued Ca2+ influx and cell migration in polyamine-deficient cells. These findings indicate that c-Jun induces PLC1 expression transcriptionally and enhances rapid epithelial restitution after injury by activating Ca2+ signal.

Source: AJP: Cell Physiology - April 1, 2017 Category: Cytology Authors: Wang, P.-Y., Wang, S. R., Xiao, L., Chen, J., Wang, J.-Y., Rao, J. N. Tags: RESEARCH ARTICLE Source Type: research