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.

拟议工作的主要主旨是在细胞水平上识别 胃和胃的表面和其他上皮细胞 十二指肠损伤，在常见情况下修复。 在日常生活中。同时，影响这种伤害的因素，既有 无论是有利的还是不利的，都将得到评估。允许的情况 或促进细胞的恢复，或那些导致坏死或 程序性细胞死亡特别令人感兴趣。最后，这一过程 表面损伤的快速修复(恢复)和以下情况 对上皮连续性恢复的影响将在 细节。 调查将针对以下方面：a)进一步 对快速上皮修复(恢复)过程的了解 特别提到细胞内pH、生长因子和 细胞外基质。具体地说，将测试以下各项： Na+/H+逆向转运蛋白的激活是否对细胞迁移是必需的 (恢复原状)发生；是否有促进生长因素的作用 修复是通过刺激Na+/H+逆向转运蛋白来实现的； 细胞外基质的各种成分是否通过以下方式影响修复 影响Na+/H+逆向转运蛋白。B)从形态上定义和定义 胃粘膜上皮细胞的生化差异 坏死性细胞死亡和程序性细胞死亡。C)评估 胃粘膜上皮损伤类型的可逆性 在日常生活中或由于感染引起的，如由 幽门螺杆菌及其免疫保护机制的研究 这样的伤害。