Proteome analysis of serum from type 2 diabetics with nephropathy
Proteome analysis of serum from type 2 diabetics with nephropathy
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DOI：
10.1021/pr060489g
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Kim, Chan-Wha
中科院分区：
文献类型：
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作者：
Kim, Hyun-Jung;Cho, Eun-Hee;Kim, Chan-Wha
糖尿病肾病（DN）是一种由糖尿病引起的肾脏疾病。微量白蛋白尿是DN最早的临床表现。除了微量白蛋白尿和大量白蛋白尿外，没有特异性诊断2型糖尿病肾病的生物标志物。然而，微量白蛋白尿并不构成2型糖尿病肾病的唯一独立指标，因此，需要另一种筛查方法，如生物标志物测定，以更准确地诊断它。因此，我们利用双向电泳（2-DE）来鉴定人血清蛋白标志物，通过比较三个实验组中的血清蛋白质组，更特异和准确地预测2型糖尿病患者的进展性肾病：无微量白蛋白尿（DM，n = 30）、有微量白蛋白尿（MA，n = 29）和有慢性肾衰竭（CRF，n = 31）的2型糖尿病患者。结果，差异表达的蛋白质具有统计学意义（p <0.05）。在这些鉴定的蛋白质中，通过蛋白质印迹法验证了可能用作2型糖尿病肾病诊断生物标志物的两种蛋白质：发现MA和CRF组细胞外谷胱甘肽过氧化物酶（eGPx）和载脂蛋白（ApoE）表现出进行性降低。值得注意的是，使用DM（n = 100）和MA（n = 96）患者样品通过ELISA进一步验证eGPx。总的来说，我们的研究结果表明，在这项研究中确定的两种蛋白质可能构成潜在的生物标志物诊断2型糖尿病肾病。
Diabetic nephropathy (DN) is a renal disease which develops as a consequence of diabetes mellitus. Microalbuminuria is the earliest clinical sign of DN. There are no specific diagnostic biomarkers for type 2 diabetics with nephropathy other than microalbuminuria and macroalbuminuria. However, microalbuminuria does not constitute a sole independent indicator for type 2 diabetics with nephropathy, and thus, another screening method, such as a biomarker assay, is required in order to diagnose it more correctly. Therefore, we have utilized two-dimensional electrophoresis (2-DE) to identify human serum protein markers for the more specific and accurate prediction of progressive nephropathy in type 2 diabetes patients, via comparisons of the serum proteome in three experimental groups: type 2 diabetes patients without microalbuminuria (DM, n = 30), with microalbuminuria (MA, n = 29), and with chronic renal failure (CRF, n = 31). As a result, proteins which were differentially expressed with statistical significance (p < 0.05) in MA and CRF groups as compared to those in DM group were selected and identified by ESI-Q-TOF MS/MS. Among these identified proteins, two proteins which might be useful as diagnostic biomarkers of type 2 diabetics with nephropathy were verified by Western blotting: extracellular glutathione peroxidase (eGPx) and apolipoprotein (ApoE) were found to exhibit a progressive reduction in MA and CRF groups. Notably, eGPx was further verified by ELISA using DM (n = 100) and MA (n = 96) patient samples. Collectively, our results show that the two proteins identified in this study may constitute potential biomarkers for the diagnosis of type 2 diabetics with nephropathy.