Journal
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
Volume 312, Issue 4, Pages C367-C375Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00330.2016
Keywords
intestinal epithelial cells; Ca2+ influx; epithelial restitution; AP-1 gene transcription; polyamines
Categories
Funding
- Department of Veterans Affairs
- National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [DK-57819, DK-61972, DK-68491]
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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-gamma 1 (PLC gamma 1) 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 PLC gamma 1 expression and enhances PLC gamma 1-induced Ca2+ signaling, thus promoting intestinal epithelial restitution after wounding. Ectopically expressed c-Jun increased PLC gamma 1 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 PLC gamma 1 promoter. Increased levels of PLC gamma 1 by c-Jun elevated cytosolic free Ca2+ concentration and stimulated intestinal epithelial cell migration over the denuded area after wounding. The c-Jun-mediated PLC gamma 1/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 PLC gamma 1 expression transcriptionally and enhances rapid epithelial restitution after injury by activating Ca2+ signal.
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