GI MUCOSAL BARRIER IN HEALTH AND SURGICAL DISEASE

健康和外科疾病中的胃肠道粘膜屏障

• 批准号: 6024412
• 负责人: Susan J Hagen
• 金额: $ 2.18万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6024412
• 关键词: BCL2 gene /protein; CD95 molecule; Helicobacter; acid base balance; adenosine triphosphate; ammonia; apoptosis; biological signal transduction; cell biology; cell migration; cell morphology; cytotoxicity; electron microscopy; gastric mucosa; gastrointestinal infection; guinea pigs; host organism interaction; immunocytochemistry; intestinal mucosa; laboratory rabbit; mitochondria; necrosis; tissue /cell culture; wound healing

The major thrust of the proposed work is to identify at cellular level the mechanisms by which surface and other epithelial cells of the stomach and duodenum are injured and are repaired in circumstances commonly encountered in daily life. Simultaneously, factors which affect such injuries, both favorably and adversely, will be evaluated. The circumstances which allow or facilitate recovery of a cell, or those which lead to necrosis or programmed cell death are of special interest. Finally, the process of rapid repair of superficial injuries (restitution) and conditions which influence this restitution of epithelial continuity will be examined in detail. The investigations will be directed toward the following: a) To further understanding of the process of rapid epithelial repair (restitution) with particular reference to the role of intracellular pH, growth factors, and the extracellular matrix. Specifically, the following will be tested: whether activation of the Na+/H+ antiporter is essential for cell migration (restitution) to occur; whether the effect of growth factors to facilitate restitution is mediated by stimulation of the Na+/H+ antiporter; and whether various components of extracellular matrix influence restitution by affecting the Na+/H+ antiporter. b) To define both morphologically and biochemically in gastric mucosal epithelial cells differences between necrotic cell death and programmed cell death. c) To evaluate the reversibility of gastric mucosal epithelial injury of the type encountered in daily living or as a result of an infection such as that caused by Helicobacter pylori and to investigate mechanisms of protection against such injuries.

这项工作的主要目的是在细胞水平上识别 胃的表面和其他上皮细胞以及 十二指肠受伤，并在通常遇到的情况下进行修复 在日常生活中同时，影响这种伤害的因素， 有利和不利的，将被评估。允许的情况 或促进细胞的恢复，或导致坏死的那些， 程序性细胞死亡是特别令人感兴趣的。最后， 快速修复表面损伤（恢复）和条件， 影响这种上皮连续性的恢复将在 详细 调查将针对以下方面：a）进一步 了解快速上皮修复（恢复）的过程， 特别提到细胞内pH、生长因子和 细胞外基质具体而言，将测试以下内容： Na+/H+逆向转运蛋白的激活是否是细胞迁移所必需的 （恢复原状）发生;是否影响生长因素，以促进 恢复由Na+/H+反向转运蛋白的刺激介导;和 细胞外基质的各种成分是否通过 影响Na+/H+逆向转运蛋白。B）从形态学和 在胃粘膜上皮细胞中的差异 坏死性细胞死亡和程序性细胞死亡。（三）评价 胃粘膜上皮损伤类型的可逆性 在日常生活中或由于感染，如由 幽门螺杆菌，并探讨保护机制， 这样的伤害。