Wang Peng-Yuan, Wang Shelley R, Xiao Lan, Chen Jie, Wang Jian-Ying, Rao Jaladanki N
Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland.
Baltimore Veterans Affairs Medical Center, Baltimore, Maryland.
Am J Physiol Cell Physiol. 2017 Apr 1;312(4):C367-C375. doi: 10.1152/ajpcell.00330.2016. Epub 2017 Jan 18.
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 Ca 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 Ca 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 Ca concentration and stimulated intestinal epithelial cell migration over the denuded area after wounding. The c-Jun-mediated PLCγ1/Ca signal also plays an important role in polyamine-induced cell migration after wounding because increased c-Jun rescued Ca 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 Ca signal.
c-Jun是一种活化蛋白1（AP-1）转录因子，参与细胞功能的多个方面，但其在损伤后早期肠上皮修复调控中的具体作用仍 largely未知。磷脂酶C-γ1（PLCγ1）催化磷脂酰肌醇4,5-二磷酸水解为第二信使二酰甘油和肌醇1,4,5-三磷酸，协调钙库动员，并在应激反应中调节细胞迁移和增殖。在此我们报道，c-Jun上调PLCγ1表达并增强PLCγ1诱导的钙信号，从而促进创伤后肠上皮修复。异位表达的c-Jun在转录水平上增加PLCγ1表达，这种刺激是通过与位于大鼠PLCγ1启动子近端区域的AP-1和CCAAT增强子结合蛋白（C/EBP）结合位点直接相互作用介导的。c-Jun引起的PLCγ1水平升高提高了胞质游离钙浓度，并刺激创伤后肠上皮细胞在裸露区域上迁移。c-Jun介导的PLCγ1/钙信号在创伤后多胺诱导的细胞迁移中也起重要作用，因为c-Jun水平升高挽救了多胺缺乏细胞中的钙内流和细胞迁移。这些发现表明，c-Jun通过激活钙信号转录诱导PLCγ1表达并增强损伤后快速上皮修复。
