IDENTIFICATION OF MICA/B EXPRESSION IN SERA OF TYPE 2 DIABETIC PATIENTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 免疫系统可能在病理性并发症的发生发展中起重要作用。已有研究表明，糖尿病高血糖可引起多种细胞应激反应，诱导血管表达免疫细胞激活配体和其他炎症因子，进而招募和激活免疫细胞，导致各种病理并发症。我们推测，在糖尿病患者的血管和参与免疫细胞激活的其他组织中，可能诱导了两种应激诱导蛋白MHC-I类链相关基因A和B(MICA/B)的表达。MICA/B可能通过与其受体NKG2D相互作用，刺激或共刺激各种免疫细胞，如自然杀伤细胞和伽马/增量T细胞。我们已经发现糖尿病小鼠血管中NKG2D的配体上调，并希望研究MICA和B在人类糖尿病患者中是否上调。 鉴于已有研究报道MICA/B在表达时可进入循环系统，我们将采集糖尿病患者的血液样本，用抗MICA/B的特异性抗体用酶联免疫吸附试验(ELISA)检测这些血样中MICA/B蛋白的含量。这项研究有助于我们了解糖尿病患者各种病理并发症发生的分子机制，并为这些糖尿病相关并发症的进展提供生物标志物。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The immune system may play an important role in the development of the pathological complications. It has been suggested that hyperglycemia in diabetes may cause various cell stresses and induce vessels to express activating ligands for immune cells and other inflammatory factors, which in turn recruit and activate immune cells, resulting in various pathological complications. We hypothesize that a couple of stress-induced proteins, MHC class I chain-related gene A and B (MICA/B), might be induced to express in the blood vessels and other tissues involved in the activation of immune cells in diabetic patients. MICA/B may stimulate or co-stimulate various immune cells, such as natural killer cells and gamma/delta T cells, through interaction with their receptor, NKG2D. We have found that upregulation of ligands for NKG2D in blood vessels of diabetic mice and would like to study whether MICA and B are upregulated in human diabetic patients. Since it has been reported that MICA/B could shed into the circulatory system when expressed, we will collect blood samples from diabetic patients and measure amounts of MICA/B proteins in these blood samples by enzyme-linked immunosorbent assay (ELISA) with specific antibodies against MICA/B. This study may help us to understand molecular mechanisms of development of the various pathological complications in diabetic patients and could provide biomarkers for progression of these diabetes-related complications.