Role of CD98 in Intestinal Permeability

项目摘要 炎症性肠病（IBD）是一种消化道慢性炎症性疾病， 道。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病的并发症 本申请寻求扩展我们先前研究的发现， 表明CD 98在协调肠上皮事件中起重要作用。等 事件包括细胞粘附/极性、氨基酸转运和分子与细胞的直接结合。 细胞表面我们小组的研究表明，CD 98的表达在肿瘤的发生发展中起着重要作用。 IBD的发病机制我们的总体假设是结肠CD 98在启动结肠癌中起关键作用。 和肠道结肠炎本提案的初步目的是调查 通过CD 98与细菌的相互作用，丧失肠屏障功能。第二 一个具体的目的是研究CD 98在结肠粘膜上皮细胞的上调中所起的作用。 包括上皮细胞分化/极化在内的活动，这些活动反过来可能影响肠道 屏障功能最后，我们将探讨是否敲低CD 98表达，使用 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物化学，分子，纳米技术， 体内和体内技术。我们希望我们将开发治疗策略，基于 操纵结肠中的CD 98表达，以减少结肠炎并抑制结肠炎的发展。 结肠炎相关的癌症 美国有超过一百万的成人和儿童患有IBD， 并发症的条件，如结肠炎相关的癌症。新的治疗策略 基于对IBD发病机制的更好理解， 患者

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.