Role of CD98 in Intestinal Permability

描述（由申请人提供）：炎症性肠病（IBD）是消化道的慢性炎症性疾病。IBD的病因仍然知之甚少。结肠直肠癌是溃疡性结肠炎和克罗恩氏结肠炎的一种危及生命的并发症。 本申请试图扩展我们先前研究的发现，其显示CD 98在肠上皮事件的协调中起重要作用。这些事件包括细胞粘附/极性、氨基酸转运和分子与细胞表面的直接结合。本课题组的研究表明，CD 98表达在IBD的发病机制中起作用。我们的总体假设是，结肠CD 98在启动和维持肠道结肠炎中起着关键作用。该提案的最初目的是研究CD 98与细菌相互作用在肠道屏障功能丧失方面所起的作用。第二个具体目的是研究CD 98在上调结肠粘膜活动中所起的作用，包括上皮细胞分化/极化，这反过来可能影响肠屏障功能。 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，体外和体内技术。我们期望我们将开发基于操纵结肠中CD 98表达的治疗策略，以减少结肠炎并抑制结肠炎相关癌症的发展。 在美国，有超过一百万的成人和儿童患有IBD及其并发症，如结肠炎相关的癌症。基于对IBD发病机制的更好理解的新治疗策略将改善此类患者的临床护理。

DESCRIPTION (provided by applicant): 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 interactin 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.