GI MUCOSAL BARRIER IN HEALTH AND SURGICAL DISEASE

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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.