Gut: 幽门螺杆菌在gastroids和胃上皮细胞中作用于癌相关顶端连接结构

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中文版

Gut

幽门螺杆菌在gastroids和胃上皮细胞中作用于癌相关顶端连接结构
 

目的:表达CagA癌蛋白的幽门螺杆菌菌株可增加胃癌的风险。然
而,
cag+菌株增加胃癌风险的具体机制尚未阐明,胃微环境的模型系统对于理解发病机制非常重要。Gastroids是三维的模拟器官的临床前模型,为研究宿主-幽门螺杆菌相互作用提供了独特的机会。笔者团队使用gastroids来解答和指导体外试验去明确幽门螺杆菌调节表达癌相关紧密连接蛋白claudin-7的机制。
 

方法:笔者团队使用腔内微注射的方法感染GastroidsMKN28胃上皮细胞分别与幽门螺杆菌野生cag+菌株或等基因突变菌株共培养。使用免疫细胞化学的方法测定β-cateninclaudin-7snail的位置,用5-乙炔基-2’-脱氧尿苷评价细胞增殖,应用蛋白质印迹和流式细胞术测定claudin-7snail的水平。
 

结果:Gastroids可发育为自我组织的分化轴,并且幽门螺杆菌以CagAβ-catenin依赖的方式诱导claudin-7错位和促进细胞增殖。在MKN28细胞内,幽门螺杆菌对claudin-7的抑制受β-cateninsnail的调节。同样的,在幽门螺杆菌感染的个体,snail的表达增加并且claudin-7的水平降低。
 

结论:gastroid系统中,幽门螺杆菌以菌株特异的方式促进细胞增殖。无论是gastroids还是人体上皮细胞中,幽门螺杆菌改变claudin-7的表达和定位,这个过程受到β-cateninsnail的调节。这些结果为研究胃微环境下幽门螺杆菌与上皮细胞在致癌过程中的分子相互作用提供了新视角。

摘自:Gut. 2015 May;64(5):720-30

原文链接:http://gut.bmj.com/content/64/5/720.long

 

英文版

Gut

Helicobacter pylori targets cancer-associated apical-junctional constituents ingastroids and gastric epithelial cells
 

OBJECTIVE: Helicobacter pylori strains that express the oncoprotein CagA augment riskfor gastric cancer. However, the precise mechanisms through which cag(+)strains heighten cancer risk have not been fully delineated and model systemsthat recapitulate the gastric niche are critical for understandingpathogenesis. Gastroids are three-dimensional organ-like structures thatprovide unique opportunities to study host-H. pylori interactions in apreclinical model. We used gastroids to inform and direct in vitro studies todefine mechanisms through which H. pylori modulates expression of thecancer-associated tight junction protein claudin-7.
 

DESIGN: Gastroids were infected by luminal microinjection, and MKN28 gastricepithelial cells were cocultured with H. pylori wild-type cag(+) strains orisogenic mutants. β-catenin, claudin-7 and snail localisation was determined byimmunocytochemistry. Proliferation was assessed using5-ethynyl-2'-deoxyuridine, and levels of claudin-7 and snail were determined bywestern blot and flow cytometry.
 

RESULTS: Gastroids developed into a self-organising differentiation axis and H.pylori induced mislocalisation of claudin-7 and increased proliferation in aCagA- and β-catenin-dependent manner. In MKN28 cells, H pylori-inducedsuppression of claudin-7 was regulated by β-catenin and snail. Similarly, snailexpression was increased and claudin-7 levels were decreased among H.pylori-infected individuals.
 

CONCLUSIONS: H. pylori increase proliferation in a strain-specificmanner in a novel gastroid system. H. pylori also alter expression andlocalisation of claudin-7 in gastroids and human epithelial cells, which ismediated by β-catenin and snail activation. These data provide new insightsinto molecular interactions with carcinogenic potential that occur between H.pylori and epithelial cells within the gastric niche.

FromGut. 2015 May;64(5):720-30

Original connectionhttp://gut.bmj.com/content/64/5/720.long

 
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