CD44 MOLECULE VARIANT EXPRESSION IN AUTOIMMUNE DIABETES

自身免疫性糖尿病中的 CD44 分子变异表达

• 批准号: 2471152
• 负责人: MIRIAM D ALONSO
• 金额: $ 7.11万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2471152
• 关键词: CD44 molecule; NOD mouse; animal genetic material tag; autoantigens; autoimmunity; diabetes mellitus genetics; gene induction /repression; insulin dependent diabetes mellitus; lymphocyte; molecular cloning; pancreatic islets; protein isoforms; recombinant proteins; tissue /cell culture

DESCRIPTION (Taken from the applicant's Abstract) Invasion of leukocytes into the pancreatic islets and the selective destruction of the insulin-secreting beta cell characterize the autoimmune disorder insulin-dependent diabetes mellitus (IDDM). The objective of this proposal is to investigate the role of the adhesion molecule CD44 in the mechanism by which lymphocyte invasion of the islet is initiated resulting in the eventual destruction of the beta cell. CD44 is a surface glycoprotein with homology to cartilage link protein, that is heavily modified post-transcriptionally, with the capability to incorporate glycoaminoglycans. The CD44 molecule presents variations in the primary structure known as isoforms, generated by a RNA alternative splicing mechanism. Based on preliminary results obtained in the non-obese diabetic mice (NOD), we hypothesize that a specific subset of CD44 isoforms may be involved in delivering key signals for lymphocyte recruitment into the islets. We propose first to extend our preliminary data by determining which combinations of CD44 isoforms are expressed by islets cells at different stages of insulitis. Second to explore the pattern of expression of CD44 variants in islet infiltrating lymphocytes at different stages of insulitis. Finally we want to search for potential ligands of the predominant subsets of CD44 variants expressed by infiltrating leukocytes. We hope that the studies that comprise this proposal will help to elucidate the molecular determinants responsible for insulitis and beta cell directed autoimmunity.

描述(摘自申请人的摘要) 白细胞对胰岛的侵袭及其选择性 自身免疫的特征是破坏了分泌胰岛素的β细胞 胰岛素依赖型糖尿病(IDDM)。这样做的目的是 建议研究黏附分子CD44在慢性粒细胞白血病中的作用 淋巴细胞侵袭胰岛的启动机制 最终破坏了β细胞。CD44是一种表面 与软骨连接蛋白同源的糖蛋白，这是严重的 转录后修改，能够合并 糖胺多聚糖。CD44分子在初级 被称为异构体的结构，由RNA选择性剪接产生 机制。基于在非肥胖型糖尿病患者中获得的初步结果 小鼠(NOD)，我们假设CD44亚型的一个特定子集可能是 参与传递淋巴细胞募集的关键信号到 小岛。我们建议首先通过确定以下内容来扩展我们的初步数据 胰岛细胞表达CD44亚型的哪些组合 不同阶段的胰岛炎症。第二，探索表达方式 急性胰腺炎不同阶段胰岛浸润性淋巴细胞中CD44变异体的表达 胰岛炎症。最后，我们想要寻找潜在的配体 CD44变异体的优势亚群由浸润性白细胞表达。 我们希望，组成这项提案的研究将有助于澄清 胰岛炎症的分子决定因素和β细胞导向 自身免疫力。