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Function analysis of Helicobacter pylori cag pathogenicity island

幽门螺杆菌cag致病岛的功能分析

基本信息

批准号：
13670502
负责人：
AZUMA Takeshi
金额：
$ 2.56万
依托单位：
Fukui Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670502/
关键词：
Helicobacter pylori Cag A pathogenicity island H.pylori cagA

项目摘要

The diversity of the CagA phosphorylation site, which determines the binding affinity of CagA to SHP-2, is suspected to be an important variable in determining the clinical outcome of Helicobacter pylori infection. In this work, we investigated the diversity of CagA in isolates from two different areas in Japan (Fukui and Okinawa), where gastric cancer risk is different, and examined the relationship between the diversity and clinical outcome. A total of 158 clinical isolates (92 Fukui strains and 66 Okinawa strains) was subjected to sequence analysis of the cagA gene. We also examined the relationship between histological features and diversity of CagA. The CagA phosphorylation and the binding affinity of CagA to SHP-2 were also examined by in vitro infection using human gastric epithelial AGS cells. Almost all (98.9%) Fukui and 68.2% of Okinawa strains possessed East Asian CagA-positive strains. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in gastritis patients infected with the East Asian CagA-positive strain than in gastritis patients infected with cagA-negative or Western CagA-positive strains. Furthermore, all gastric cancer strains were East Asian CagA-positive. Biochemically, the East Asian CagA protein exhibited stronger SHP-2 binding activity than the Western CagA did. These findings suggest that infection of East Asian CagA-positive H. pylori infection is substantially associated with atrophic gastritis and gastric cancer, and that persistent active inflammation induced by the East Asian CagA-positive strain, which possesses stronger SHP-2 binding activity than the Western type, may play a role in the pathogenesis of atrophic gastritis and gastric cancer.

CagA磷酸化位点的多样性决定了CagA与SHP-2的结合亲和力，被怀疑是决定幽门螺杆菌感染临床结果的重要变量。在这项工作中，我们调查了CagA的多样性，在日本的两个不同地区（福井和冲绳），胃癌的风险是不同的分离株，并检查多样性和临床结果之间的关系。对总共158个临床分离株（92个福井菌株和66个冲绳菌株）进行cagA基因的序列分析。我们还研究了组织学特征和CagA多样性之间的关系。体外感染人胃上皮AGS细胞，检测CagA的磷酸化及CagA与SHP-2的结合亲和力。福井和冲绳的CagA阳性率分别为98.9%和68.2%。感染东亚CagA阳性菌株的胃炎患者的炎症、胃炎活动性和萎缩程度显著高于感染cagA阴性或西方CagA阳性菌株的胃炎患者。此外，所有胃癌菌株均为东亚CagA阳性。在生物化学上，东亚CagA蛋白表现出比西方CagA更强的SHP-2结合活性。这些结果表明，东亚CagA阳性H。pylori感染与萎缩性胃炎和胃癌密切相关，并且由东亚CagA阳性菌株诱导的持续活性炎症可能在萎缩性胃炎和胃癌的发病机制中起作用，该菌株具有比西方型更强的SHP-2结合活性。