幽门螺杆菌对体外胃上皮细胞迁移和增殖的影响：空泡毒素A（VacA）和细胞毒素相关蛋白A（CagA）的作用
Effect of Helicobacter pylori on gastric epithelial cell migration and proliferation in vitro: role of VacA and CagA.
作者信息
Ricci V, Ciacci C, Zarrilli R, Sommi P, Tummuru M K, Del Vecchio Blanco C, Bruni C B, Cover T L, Blaser M J, Romano M
机构信息
Istituto di Fisiologia Umana, Università di Pavia, Italy.
出版信息
Infect Immun. 1996 Jul;64(7):2829-33. doi: 10.1128/iai.64.7.2829-2833.1996.
Abstract
Helicobacter pylori infection is associated with inflammation of the gastric mucosa and with gastric mucosal damage. In this study, we sought to test the hypothesis that two H. pylori virulence factors (VacA and CagA) impair gastric epithelial cell migration and proliferation, the main processes involved in gastric mucosal healing in vivo. Human gastric epithelial cells (MKN 28) were incubated with undialyzed or dialyzed broth culture filtrates from wild-type H. pylori strains or isogenic mutants defective in production of VacA, CagA, or both products. We found that (i) VacA specifically inhibited cell proliferation without affecting cell migration, (ii) CagA exerted no effect on either cell migration or proliferation, and (iii) undialyzed H. pylori broth culture filtrates inhibited both cell migration and proliferation through a VacA- and CagA-independent mechanism. These findings demonstrate that, in addition to damaging the gastric mucosa, H. pylori products may also impair physiological processes required for mucosal repair.
摘要
幽门螺杆菌感染与胃黏膜炎症及胃黏膜损伤有关。在本研究中，我们试图验证以下假设：两种幽门螺杆菌毒力因子（VacA和CagA）会损害胃上皮细胞迁移和增殖，而这是体内胃黏膜愈合的主要过程。将人胃上皮细胞（MKN 28）与野生型幽门螺杆菌菌株或VacA、CagA或两者产物产生缺陷的同基因突变体的未透析或透析肉汤培养滤液一起孵育。我们发现：（i）VacA特异性抑制细胞增殖而不影响细胞迁移；（ii）CagA对细胞迁移或增殖均无影响；（iii）未透析的幽门螺杆菌肉汤培养滤液通过一种不依赖VacA和CagA的机制抑制细胞迁移和增殖。这些发现表明，除了损害胃黏膜外，幽门螺杆菌产物还可能损害黏膜修复所需的生理过程。
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本文引用的文献
1
Cellular responses to DNA damage: cell-cycle checkpoints, apoptosis and the roles of p53 and ATM.细胞对DNA损伤的反应：细胞周期检查点、细胞凋亡以及p53和ATM的作用。
Trends Biochem Sci. 1995 Oct;20(10):426-30. doi: 10.1016/s0968-0004(00)89093-3.
2
Transforming growth factor beta regulation of migration in wounded rat intestinal epithelial monolayers.转化生长因子β对受伤大鼠肠上皮单层细胞迁移的调控
Gastroenterology. 1993 Jul;105(1):93-101. doi: 10.1016/0016-5085(93)90014-4.
3
Cloning and expression of a high-molecular-mass major antigen of Helicobacter pylori: evidence of linkage to cytotoxin production.幽门螺杆菌一种高分子量主要抗原的克隆与表达：与细胞毒素产生相关的证据
Infect Immun. 1993 May;61(5):1799-809. doi: 10.1128/iai.61.5.1799-1809.1993.
4
Pathogenicity of Helicobacter pylori: a perspective.幽门螺杆菌的致病性：一种观点。
Infect Immun. 1993 May;61(5):1601-10. doi: 10.1128/iai.61.5.1601-1610.1993.
5
Pathogenic mechanisms of Helicobacter pylori.幽门螺杆菌的致病机制
Gastroenterol Clin North Am. 1993 Mar;22(1):43-57.
6
Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia.长期给予氨诱导大鼠胃黏膜萎缩的细胞动力学
Gastroenterology. 1993 Mar;104(3):796-801. doi: 10.1016/0016-5085(93)91015-a.
7
Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor beta.细胞因子对肠上皮细胞修复的调节作用：转化生长因子β的核心作用
Gastroenterology. 1993 Nov;105(5):1323-32. doi: 10.1016/0016-5085(93)90136-z.
8
Mutation of the cytotoxin-associated cagA gene does not affect the vacuolating cytotoxin activity of Helicobacter pylori.细胞毒素相关cagA基因的突变不影响幽门螺杆菌的空泡毒素活性。
Infect Immun. 1994 Jun;62(6):2609-13. doi: 10.1128/iai.62.6.2609-2613.1994.
9
Gene structure of the Helicobacter pylori cytotoxin and evidence of its key role in gastric disease.幽门螺杆菌细胞毒素的基因结构及其在胃部疾病中关键作用的证据。
J Exp Med. 1994 May 1;179(5):1653-58. doi: 10.1084/jem.179.5.1653.
10
Divergence of genetic sequences for the vacuolating cytotoxin among Helicobacter pylori strains.幽门螺杆菌菌株中致空泡细胞毒素基因序列的差异。
J Biol Chem. 1994 Apr 8;269(14):10566-73.
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