幽门螺杆菌通过富含 GC 的 DNA 元件诱导胃泌素启动子。
Helicobacter pylori induction of the gastrin promoter through GC-rich DNA elements.
机构信息
Departments of Internal Medicine, Microbiology and Immunology and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
出版信息
Helicobacter. 2010 Oct;15(5):438-48. doi: 10.1111/j.1523-5378.2010.00787.x.
BACKGROUND
Helicobacter pylori (H. pylori) infection has been linked to the development of chronic gastritis, duodenal ulcer disease, and gastric cancer. Helicobacter pylori- infected patients and animal models develop hypergastrinemia, chronic gastritis, and gastric atrophy. Since gastrin is an important regulator of gastric acid secretion and cell growth, H. pylori regulation of this hormone has been implicated in its pathogenesis.
OBJECTIVES
To investigate the effect of H. pylori on gastrin gene expression in mice and of human bacterial isolates on gastrin mRNA expressed in a human cell line.
METHODS
Gastrin mRNA was measured by qRT-PCR in H. pylori-infected mice. H. pylori were co-cultured with AGS cells to study regulation of human gastrin gene expression. Various MAP kinases were implicated in signal transduction from the bacteria using specific inhibitors. Gastrin reporter constructs and gel shift assays were used to map DNA responsive elements.
RESULTS
In addition to an increase in gastrin mRNA in H. pylori-infected mice, H. pylori induced the endogenous human gastrin gene through MAP kinase-dependent signaling but not NFκB-dependent signaling. Activation of gastrin through MAPK signaling did not require CagA or VacA virulence factors. Transfection studies demonstrated that a GC-rich motif mediated H. pylori-induction of the gastrin promoter and that the motif inducibly binds Sp1 and Sp3 transcription factors.
CONCLUSIONS
Direct contact of live H. pylori bacteria with human cells is sufficient to induce gastrin gene expression.
背景
幽门螺杆菌（H. pylori）感染与慢性胃炎、十二指肠溃疡病和胃癌的发展有关。H. pylori 感染的患者和动物模型会出现高胃泌素血症、慢性胃炎和胃萎缩。由于胃泌素是胃酸分泌和细胞生长的重要调节剂，因此 H. pylori 对这种激素的调节与其发病机制有关。
目的
研究 H. pylori 对小鼠胃泌素基因表达的影响，以及人类细菌分离株对人细胞系中胃泌素 mRNA 的表达的影响。
方法
通过 qRT-PCR 测量 H. pylori 感染小鼠的胃泌素 mRNA。将 H. pylori 与 AGS 细胞共培养，以研究其对人胃泌素基因表达的调节。使用特定的抑制剂来研究各种 MAP 激酶在细菌信号转导中的作用。使用胃泌素报告基因构建体和凝胶迁移分析来映射 DNA 反应元件。
结果
除了在 H. pylori 感染的小鼠中增加胃泌素 mRNA 外，H. pylori 通过 MAP 激酶依赖性信号转导诱导内源性人胃泌素基因，而不是 NFκB 依赖性信号转导。通过 MAPK 信号转导激活胃泌素不需要 CagA 或 VacA 毒力因子。转染研究表明，富含 GC 的基序介导了 H. pylori 诱导的胃泌素启动子，并且该基序可诱导 Sp1 和 Sp3 转录因子结合。
结论
活的 H. pylori 细菌与人细胞的直接接触足以诱导胃泌素基因表达。
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