Down-regulation of a morphogen (sonic hedgehog) gradient in the gastric epithelium of Helicobacter pylori-infected Mongolian gerbils
Down-regulation of a morphogen (sonic hedgehog) gradient in the gastric epithelium of Helicobacter pylori-infected Mongolian gerbils
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DOI：
10.1002/path.1763
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发表时间：
2005-06-01
影响因子：
7.3
通讯作者：
Hibi, T
中科院分区：
文献类型：
--
作者：
Suzuki, H;Minegishi, Y;Hibi, T
音猬因子（Shh）是一种形态发生素，在胚胎发生过程中参与肠道模式形成的多个方面，并且在成年个体中参与胃底腺的内稳态。胃上皮的肠化生改变与Shh表达缺失有关，缺乏Shh表达的小鼠显示胃黏膜的肠化转变。本研究旨在探讨幽门螺杆菌（H. pylori）定植实验模型中胃内Shh表达的改变。雄性蒙古沙鼠接种幽门螺杆菌，并在4周和51周后进行检查。通过定量逆转录聚合酶链反应和原位杂交测定Shh mRNA的表达水平。通过免疫印迹和免疫组织化学测定Shh蛋白的表达。Shh在沙鼠胃底腺的壁细胞、主细胞和颈黏液细胞中表达。幽门螺杆菌的长期定植导致炎症从胃窦延伸至胃体，同时Shh表达缺失。Shh表达缺失与壁细胞缺失、颈黏液细胞 - 主细胞谱系成熟紊乱以及细胞增殖增加相关。在幽门螺杆菌相关胃炎中，Shh表达显著降低。这些数据首次表明幽门螺杆菌感染导致一种在胃上皮分化中具有既定作用（Shh）的形态发生素表达下调。版权所有（c）2005英国和爱尔兰病理学会。由约翰威立父子有限公司出版。
Sonic hedgehog (Shh) is a morphogen involved in many aspects of patterning of the gut during embryogenesis and in gastric fundic gland homeostasis in the adult. Intestinal metaplastic change of the gastric epithelium is associated with the loss of Shh expression, and mice that lack Shh expression show intestinal transformation of the gastric mucosa. The present study was designed to investigate the alteration of Shh expression in the stomach of an experimental model of Helicobacter pylori (H. pylori) colonization. Male Mongolian gerbils were inoculated with H. pylori and examined 4 and 51 weeks later. The level of Shh mRNA expression was determined by quantitative RT-PCR and ill situ hybridization. Shh protein expression was determined by immunoblotting and immunohistochemistry. Shh was expressed in the parietal cells, zymogenic cells, and mucous neck cells of the gastric fundic glands of gerbils. Prolonged colonization by H. pylori led to extension of the inflammation from the antrum to the corpus of the stomach, with loss of Shh expression. Loss of Shh expression correlated with loss of parietal cells, disturbed maturation of the mucous neck cell-zymogenic cell lineage, and increased cellular proliferation. Shh expression is significantly reduced in H. pylori-associated gastritis. These data show for the first time that H. pylori infection leads to down-regulation of the expression of a morphogen with an established role (Shh) in gastric epithelial differentiation. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.