title: c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-γ1 transcription.
abstract: 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-γ1 (PLCγ1) 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 PLCγ1 expression and enhances PLCγ1-induced Ca2+signaling, thus promoting intestinal epithelial restitution after wounding. Ectopically expressed c-Jun increased PLCγ1 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 PLCγ1 promoter. Increased levels of PLCγ1 by c-Jun elevated cytosolic free Ca2+concentration and stimulated intestinal epithelial cell migration over the denuded area after wounding. The c-Jun-mediated PLCγ1/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 PLCγ1 expression transcriptionally and enhances rapid epithelial restitution after injury by activating Ca2+signal.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Wang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.|Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland; and.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland; rjaladanki@som.umaryland.edu.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D007416:Intestinal Perforation / Q000378:metabolism*; D051966:Phospholipase C gamma / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D051381:Rats; D014158:Transcription, Genetic; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D051966:Phospholipase C gamma; C000607812:phospholipase Cgamma1, rat
keywords: AP-1 gene transcription; Ca2+ influx; epithelial restitution; intestinal epithelial cells; polyamines