Vcsa1 (hSMR3A) as a Marker for Diabetes

描述（由申请人提供）：我的团队最近发现Vcsa1是糖尿病血管并发症导致勃起功能障碍（ED）的潜在生物标志物。我们发现Vcsa1是糖尿病大鼠体中下调最多的基因之一。我们还发现，该基因的潜在人类同源物（hSMR3A）在糖尿病患者体内样本中下调。我们发表的研究表明，Vcsa1 （sialorphin）的成熟肽产物在调节下体平滑肌张力中起作用，并且潜在的相同机制也可能在调节其他血管组织张力中起作用。我们假设Vcsa1（及其人类同源物hSMR3A）及其蛋白产物的表达水平可以作为糖尿病血管并发症的标志物。我们的实验旨在在动物模型和患者样本中证实这一假设。在动物实验中，我们将使用定量RT-PCR确定糖尿病如何影响血管组织中Vcsa1的表达，并将Vcsa1的表达与糖尿病的严重程度联系起来。我们还将使用免疫测定法确定糖尿病是否影响糖尿病动物血液和唾液中唾液啡肽的表达。我们的第二个目标是开发一种针对hSMR3A （Vcsa1的人类同源物）蛋白产物的抗体。使用该抗体，我们将使用MALDI-TOFF光谱研究hSMR3A产物的表达和加工。这将使我们能够开发出一种有效的用于患者的免疫测定方法。最终目的是确定糖尿病和非糖尿病患者（唾液、血液和身体样本）中hSMR3A蛋白的表达水平，作为血管健康的指标。

DESCRIPTION (provided by applicant): My group recently identified Vcsa1 as a potential biomarker for vascular complications of diabetes leading to erectile dysfunction (ED). We demonstrated that Vcsa1 is one of the most downregulated genes in the corpora of diabetic rats. We have also shown that a potential human homologue of this gene (hSMR3A) is downregulated in diabetic patient orporal samples. Our published studies demonstrate that the mature peptide product of Vcsa1 (sialorphin) plays a role in regulating corporal smooth muscle tone and potentially the same mechanisms may also function in regulating other vascular tissues tone. We hypothesize that level of expression of Vcsa1 (and its human homologue, hSMR3A) and their protein products, can act as markers for the vascular complications of diabetes. Our experiments are designed to confirm this hypothesis in animal models and from atient samples. In animal experiments we will determine how diabetes effects the expression of Vcsa1 using quantitative RT-PCR in vascular tissues and correlate the expression of Vcsa1 to the severity of diabetes We will also determine if diabetes effects the expression of sialorphin in the bloodstream and saliva of diabetic animals using immunoassays. Our second aim will be to develop an antibody against the protein product of hSMR3A (the human homologue of Vcsa1). Using this antibody we will investigate the expression and processing of the hSMR3A product using MALDI-TOFF spectroscopy. This will allow us to develop an effective immunoassay for use in patients. The final aim will be to determine expression levels of hSMR3A protein from diabetic and non-diabetic patients (in saliva, blood and corporal samples) as an indicator of vascular health.