Ludwig Maximilians University Munich, Munich, Germany.
Gut. 2012 Jul;61(7):986-96. doi: 10.1136/gutjnl-2011-300525. Epub 2012 Jan 27.
One of the most important hormones in the human stomach is the peptide gastrin. It is mainly required for the regulation of gastric pH but is also involved in growth and differentiation of gastric epithelial cells. In Helicobacter pylori infected patients, gastrin secretion can be upregulated by the pathogen, resulting in hypergastrinaemia. H pylori induced hypergastrinaemia is described as being a major risk factor for the development of gastric adenocarcinoma.
In this study, the upstream receptor complex and bacterial factors involved in H pylori induced gastrin gene expression were investigated, utilising gastric epithelial cells which were stably transfected with a human gastrin promoter luciferase reporter construct.
Integrin linked kinase (ILK) and integrin β5, but not integrin β1, played an important role in gastrin promoter activation. Interestingly, a novel CagL/integrin β5/ILK signalling complex was characterised as being important for H pylori induced gastrin expression. On interaction of H pylori with αvβ(5)-integrin and ILK, the epidermal growth factor receptor (EGFR)→Raf→mitogen activated protein kinase kinase (MEK)→extracellular signal regulated kinase (Erk) downstream signalling cascade was identified which plays a central role in H pylori gastrin induction.
The newly discovered recognition receptor complex could be a useful target in treating precancerous conditions triggered by H pylori induced hypergastrinaemia.
胃中的一种重要激素是肽胃泌素。它主要用于调节胃 pH 值，但也参与胃上皮细胞的生长和分化。在幽门螺杆菌感染的患者中，病原体可上调胃泌素的分泌，导致高胃泌素血症。幽门螺杆菌引起的高胃泌素血症被描述为胃腺癌发展的主要危险因素。
本研究利用稳定转染人胃泌素启动子荧光素酶报告构建体的胃上皮细胞，研究了幽门螺杆菌诱导胃泌素基因表达涉及的上游受体复合物和细菌因子。
整合素连接激酶（ILK）和整合素β5，但不是整合素β1，在胃泌素启动子激活中起重要作用。有趣的是，作为幽门螺杆菌诱导胃泌素表达的重要因素，我们描述了一种新型 CagL/整合素β5/ILK 信号复合物。在幽门螺杆菌与αvβ（5）-整合素和 ILK 相互作用时，鉴定出表皮生长因子受体（EGFR）→Raf→丝裂原激活蛋白激酶激酶（MEK）→细胞外信号调节激酶（Erk）下游信号级联反应，该级联反应在幽门螺杆菌诱导的胃泌素诱导中发挥核心作用。
新发现的识别受体复合物可能是治疗由幽门螺杆菌诱导的高胃泌素血症引发的癌前状态的有用靶点。
