Role of CD98 in Intestinal Permeability

项目摘要 炎症性肠病(IBD)是一种慢性消化系统炎症性疾病 一条小路。IBD的病因仍然知之甚少。结直肠癌是一种危及生命的疾病 溃疡性结肠炎和克罗恩结肠炎的并发症。 本申请旨在扩展我们先前研究的结果，该研究 表明CD98在肠道上皮细胞事件的协调中起重要作用。是这样的 这些事件包括细胞黏附/极性、氨基酸运输和分子与 细胞表面。我们课题组的研究表明，CD98的表达在血管内皮细胞生长中起作用。 IBD的发病机制。我们的总体假设是，结肠CD98在启动 和永久性的肠结肠炎。这项建议的最初目的是调查所扮演的角色 通过CD98与细菌的相互作用导致肠道屏障功能的丧失。第二 目的：探讨CD98在结肠粘膜上调中的作用。 包括上皮细胞分化/极化在内的活动，进而可能影响肠道 屏障功能。最后，我们将使用一个 有针对性的纳米技术方法，减少结肠炎和结肠炎相关癌症的程度。 拟议的项目将使用各种生化、分子、纳米技术，例如 活体和活体技术。我们预计，我们将制定治疗策略，基于 调控CD98在结肠中的表达，减轻结肠炎和抑制结肠炎的发展 结肠炎相关癌症。 美国有100多万成年人和儿童患有IBD和 疾病的并发症，如结肠炎相关癌症。新的治疗策略 基于对IBD发病机制的更好认识，将提高此类患者的临床护理水平 病人。

Project Summary Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the digestive tract. The etiology of IBD remains poorly understood. Colorectal cancer is a life-threatening complication of both ulcerative and Crohn's colitis. The present application seeks to extend the findings of our previous studies, which showed that CD98 plays an important role in coordination of intestinal epithelial events. Such events include cell adhesion/polarity, amino acid transport, and direct binding of molecules to cell surfaces. Studies by our group have shown that CD98 expression plays a role in the pathogenesis of IBD. Our overall hypothesis is that colonic CD98 plays a critical role in initiating and perpetuating intestinal colitis. The initial aim of this proposal is to investigate the role played by interaction of CD98 with bacteria in terms of the loss of intestinal barrier function. The second specific aim is to investigate the role played by CD98 in upregulation of colonic mucosal activities including epithelial cell differentiation/polarization that may, in turn, affect intestinal barrier function. Finally, we will explore whether knockdown of CD98 expression, using a targeted nanotechnological approach, reduces the extent of colitis and colitis-associated cancer. The proposed project will use a variety of biochemical, molecular, nanotechnological, ex vivo, and in vivo techniques. We expect that we will develop therapeutic strategies, based on manipulation of CD98 expression in the colon, to reduce colitis and to inhibit development of colitis-associated cancer. More than one million adults and children in the United States suffer from IBD and complications of the condition, such as colitis-associated cancer. New therapeutic strategies based on a better understanding of IBD pathogenesis will improve the clinical care of such patients.