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DIVERSIFIED ANALYSIS OF GASTRICMUCOSA

胃粘膜多样化分析

基本信息

批准号：
18590671
负责人：
ISHIKAWA Takashi
金额：
$ 2.49万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590671/
关键词：
Histamin H2 receptor Knock out mouse Gastric mucosa Ghrelin Sonic hedgehog Gastric acid secvetion A fundus ventriculiglad mucous mem brane 胃粘膜

项目摘要

Gastric acid secretion is regulated through the surface receptors for hisitamine, gastrin, and acetylcholine on parietal cells of the gastric oxyntic mucosa. Ghreline, a novel growth hormone-releasing peptide, is considered as one of the stimulants of acid secretion by the gastric mucosa. In H2R-null mice, the effect of so-called receptor upregulation is excluded as a causative factor for the decrease in the antisecretory effect because the H2R deficiency is congenital. One of the study was designed to investigate the relation between acid secretion and ghreline expression, which is independent of histamine, by using H2R-null mice. The experiments showed that ghreline production and secretion in the gastric mucosa were enhanced in genetic H2R knockout mice, suggesting that ghreline can promote acid secretion under particular conditions of the absence of a hisitamine-dependent pathway for acid secretion.Expression of the sonic hedgehog (Shh), a morphogen for the gastric fundic glands, i … More s reduced in the atrophic mucosa that develops in association with Helicobacter pylon infection, resulting impaired differentiation of the fundic gland cells, increased expression of trefoil factor family 2 (TEF2) and the formation of spasmotlytic polypeptide expressing metaplasia, a preneoplastic lesion. To study the effects of acid exposure, HCL solution was administered to the H2R-null mice. These mice exhibited higher gastric pH, increased TEF2 expression and reduced Shh expression. Our results suggest that persistent parietal cell dysfunction may be sufficient to down-regulate Shh expression in TEF-2 overexpressing preneoplatic lesions of the gastric fundus. Since exposure to acid restored fundic Shh expression, appropriate gastric acid secretion may play an important role in the morphogen dynamics involved in the maintenance of gastric fundic gland homeostasis. Our findings have revealed that down-regulation of Shh expression can be evoked not only by the parietal cell loss associated with H pylon infection, but also by parietal cell dysfunction in the absence of inflammation and/or parietal loss. Our results suggest the important role of optimal gastric acid secretion, an important parameter of gastric Shh expression and in gastric gland homeostasis. Less

胃酸分泌通过胃泌酸粘膜壁细胞上组胺、胃泌素和乙酰胆碱的表面受体调节。Ghreline是一种新的生长激素释放肽，被认为是胃粘膜泌酸的刺激物之一。在H2 R缺失小鼠中，由于H2 R缺陷是先天性的，因此排除了所谓的受体上调效应作为抗分泌效应降低的致病因素。其中一项研究旨在通过使用H2 R缺失小鼠来研究酸分泌和生长激素肽表达之间的关系，其不依赖于组胺。实验表明，在H2 R基因敲除小鼠中，胃粘膜中生长激素肽的产生和分泌增强，表明生长激素肽在缺乏组胺依赖性胃酸分泌途径的特定条件下可以促进胃酸分泌。 ...更多信息在与幽门螺杆菌感染相关的萎缩性粘膜中减少，导致胃底腺细胞分化受损，三叶因子家族2（TEF 2）表达增加和形成表达解痉多肽的化生（一种癌前病变）。为了研究酸暴露的影响，将HCL溶液施用于H2 R缺失小鼠。这些小鼠表现出更高的胃pH值，增加TEF 2表达和减少Shh表达。我们的研究结果表明，持续的壁细胞功能障碍可能足以下调Shh表达TEF-2过度表达癌前病变的胃底。由于暴露于酸恢复胃底Shh的表达，适当的胃酸分泌可能发挥重要作用的形态动力学参与维持胃底腺的稳态。我们的研究结果表明，Shh表达的下调不仅可以诱发壁细胞损失与H pylon感染，但也由壁细胞功能障碍的情况下，炎症和/或壁损失。我们的研究结果表明，最佳胃酸分泌的重要作用，一个重要的参数，胃Shh的表达和胃腺的稳态。少