Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle.
Helicobacter pylori strain-specific genotypes and modulation of the gastric epithelial cell cycle.
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发表时间：
1999-12
期刊：
影响因子：
11.2
通讯作者：
R. Peek;M. Blaser;D. Mays;M. H. Forsyth;T. Cover;S. Song;U. Krishna;J. Pietenpol
中科院分区：
文献类型：
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作者：
R. Peek;M. Blaser;D. Mays;M. H. Forsyth;T. Cover;S. Song;U. Krishna;J. Pietenpol
幽门螺杆菌cag+菌株在体内增强胃上皮细胞增殖并减弱凋亡，这可能部分解释了与这些菌株相关的胃癌风险增加。本研究的目的是确定特定的H。pylori基因调控上皮细胞周期事件，并确定这些作用是否依赖于p53介导的途径。AGS胃上皮细胞单独培养或在21种临床H. pylori分离株、H. pylori参考菌株60190或其同基因cagA-、picB-、vacA-或picB-/vacA-衍生物。共培养H. pylori感染AGS细胞显著降低细胞活力，cag+菌株的效果最显著（P < 0.001，相对于cag-菌株）。cag+菌株在6 h显著促进AGS细胞从G1期向G2-M期的进展，并在72 h促进凋亡。与亲本60190株相比，picB-突变株在6 h时细胞周期进程减慢（P <或= 0.05），在24 h时细胞凋亡减少，细胞活力增强（P <或= 0.04）。vacA-突变体在随后的时间点（48-72小时）减少细胞凋亡并增强存活力（P <或= 0.05）。与野生型相比，picB-/vacA-双突变株在所有时间点均显著减少细胞凋亡，提高细胞活力（P <或= 0.05）。此外，与H. pylori对p53、p21和MDM 2的表达无明显影响。cag+ H可降低AGS细胞活力，使其进展至G2-M期，并导致细胞凋亡。pylori菌株依赖于vacA和cag致病岛内基因的表达。这些结果可以解释在H.幽门结肠化粘膜
Helicobacter pylori cag+ strains enhance gastric epithelial cell proliferation and attenuate apoptosis in vivo, which may partially explain the increased risk of gastric cancer associated with these strains. The goals of this study were to identify specific H. pylori genes that regulate epithelial cell cycle events and determine whether these effects were dependent upon p53-mediated pathways. AGS gastric epithelial cells were cultured alone or in the presence of 21 clinical H. pylori isolates, H. pylori reference strain 60190, or its isogenic cagA-, picB-, vacA-, or picB-/vacA- derivatives. Coculture of H. pylori with AGS cells significantly decreased cell viability, an effect most prominent with cag+ strains (P < 0.001 versus cag-strains). cag+ strains significantly increased progression of AGS cells from G1 into G2-M at 6 h and enhanced apoptosis by 72 h. Compared with the parental 60190 strain, the picB- mutant attenuated cell cycle progression at 6 h (P < or = 0.05), and decreased apoptosis with enhanced AGS cell viability at 24 h (P < or = 0.04). The vacA- mutant decreased apoptosis and enhanced viability at later (48-72 h) time points (P < or = 0.05). Compared with the wild-type strain, the picB-/vacA- double mutant markedly attenuated apoptosis and increased cell viability at all time points (P < or = 0.05). Furthermore, cocolonization with H. pylori had no significant effect on expression of p53, p21, and MDM2. The diminished AGS cell viability, progression to G2-M, and apoptosis associated with cag+ H. pylori strains were dependent upon expression of vacA and genes within the cag pathogenicity island. These results may explain heterogeneity in levels of gastric epithelial cell proliferation and apoptosis found within H. pyloricolonized mucosa.