Regulation of mammalian gastrin/CCK receptor (CCK2R) expression in vitro and in vivo.
Regulation of mammalian gastrin/CCK receptor (CCK2R) expression in vitro and in vivo.
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DOI：
10.1113/expphysiol.2007.040683
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发表时间：
2008-02
影响因子：
2.7
通讯作者：
Dimaline, Rod
中科院分区：
文献类型：
--
作者：
Ashurst, H. Louise;Varro, Andrea;Dimaline, Rod
胃泌素/CCK受体（gastrin/CCK receptor, CCK2R）介导胃泌素的生理功能，包括刺激胃酸分泌和细胞增殖和迁移，但对其表达的调控因素知之甚少。我们在几种细胞系中发现了内源性CCK2R的表达，并使用荧光素酶启动子报告子构建物来确定人胃腺癌AGS和大鼠胃粘膜RGM1细胞转录所需的最小启动子。SP1、C/EBP和GATA的一致结合位点对活性至关重要。从RGM1和AR42J细胞中提取血清后，内源性CCK2R mRNA丰度和CCK2R启动子报告结构的活性显著升高。胃泌素也通过部分依赖于蛋白激酶C （PKC）和丝裂原/细胞外信号调节激酶（MEK）的机制，在AGS-GR和RGM1细胞中增加CCK2R的转录。胃泌素显著提高RGM1细胞内源性CCK2R表达，高胃泌血症动物胃中CCK2R蛋白表达升高。在分泌酸粘膜有低温损伤的小鼠中，CCK2R表达在溃疡修复边缘附近的再生粘膜中逐渐增加，在损伤后6天明显，在13天达到最大。CCK2R在溃疡修复后6-9天的粘膜下层重新表达。许多粘膜和粘膜下层细胞在低温损伤下表达CCK2R，被鉴定为肌成纤维细胞，因为它们共同表达vimentin和平滑肌α-actin，而不表达desmin。这些数据表明，CCK2R表达的增加可能影响上皮炎症或损伤的结果，并且这种反应可能部分由肌成纤维细胞介导。
The gastrin/CCK receptor (CCK2R) mediates the physiological functions of gastrin in the stomach, including stimulation of acid secretion and cellular proliferation and migration, but little is known about the factors that regulate its expression. We identified endogenous CCK2R expression in several cell lines and used luciferase promoter–reporter constructs to define the minimal promoter required for transcription in human gastric adenocarcinoma, AGS, and rat gastric mucosa, RGM1, cells. Consensus binding sites for SP1, C/EBP and GATA were essential for activity. Following serum withdrawal from RGM1 and AR42J cells, endogenous CCK2R mRNA abundance and the activity of a CCK2R promoter–reporter construct were significantly elevated. Transcription of CCK2R was also increased in AGS-GR and RGM1 cells by gastrin through mechanisms partly dependent upon protein kinase C (PKC) and mitogen/extracellular signal-regulated kinase (MEK). Gastrin significantly increased endogenous CCK2R expression in RGM1 cells, and CCK2R protein expression was elevated in the stomach of hypergastrinaemic animals. In mice with cryoulcers in the acid-secreting mucosa, CCK2R expression increased progressively in the regenerating mucosa adjacent to the ulcer repair margin, evident at 6 days postinjury and maximal at 13 days. De novo expression of CCK2R was observed in the submucosa beneath the repairing ulcer crater 6–9 days postinjury. Many of the cells in mucosa and submucosa that expressed CCK2R in response to cryoinjury were identified as myofibroblasts, since they coexpressed vimentin and smooth muscle α-actin but not desmin. The data suggest that increased CCK2R expression might influence the outcome of epithelial inflammation or injury and that the response may be mediated in part by myofibroblasts.
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影响因子：
8
作者：
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通讯作者：
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影响因子：
29.4
作者：
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10.1152/ajpgi.1998.274.3.g561
发表时间：
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影响因子：
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