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1 型糖尿病肾病患者血清中纤维蛋白肽 A 及其相关片段的不同表达。

Different expression of fibrinopeptide A and related fragments in serum of type 1 diabetic patients with nephropathy.

机构信息

Department of Experimental Medicine, University of Milano-Bicocca, via Cadore 48, 20052 Monza, Italy.

出版信息

J Proteomics. 2010 Jan 3;73(3):593-601. doi: 10.1016/j.jprot.2009.07.006. Epub 2009 Jul 23.

Abstract

Type 1 diabetes (insulin-dependent diabetes mellitus, IDDM) is an autoimmune disease affecting about 0.12% of the world's population. Diabetic nephropathy (DN) is a major long-term complication of both types of diabetes and retains a high human, social and economic cost. Thus, the identification of markers for the early detection of DN represents a relevant target of diabetic research. The present work is a pilot study focused on proteomic analysis of serum of controls (n=9), IDDM patients (n=10) and DN patients (n=4) by the ClinProt profiling technology based on mass spectrometry. This approach allowed to identify a pattern of peptides able to differentiate the studied populations with sensitivity and specificity close to 100%. Variance of the results allowed to estimate the sample size needed to keep the expected False Discovery Rate low. Moreover, three peptides differentially expressed in the serum of patients as compared to controls were identified by LC-ESI MS/MS as the whole fibrinopeptide A peptide and two of its fragments, respectively. The two fragments were under-expressed in diabetic patients, while Fibrinopeptide A was over-expressed, suggesting that anomalous turnover of Fibrinopeptide A could be involved in the pathogenesis of DN.

摘要

1 型糖尿病(胰岛素依赖型糖尿病,IDDM)是一种影响全球约 0.12%人口的自身免疫性疾病。糖尿病肾病(DN)是两种类型糖尿病的主要长期并发症,并保留了高的人类,社会和经济成本。因此,鉴定用于早期检测 DN 的标志物代表了糖尿病研究的一个相关目标。本工作是一项初步研究,重点是通过基于质谱的 ClinProt 分析技术对对照者(n=9)、1 型糖尿病患者(n=10)和 DN 患者(n=4)的血清进行蛋白质组分析。该方法能够识别出一种肽模式,其能够以接近 100%的灵敏度和特异性来区分研究人群。结果的变异性允许估计保持预期假发现率低所需的样本量。此外,通过 LC-ESI MS/MS 鉴定了在患者血清中与对照相比差异表达的三种肽,分别为全长纤维蛋白肽 A 肽及其两个片段。在糖尿病患者中,两种片段表达下调,而纤维蛋白肽 A 表达上调,这表明纤维蛋白肽 A 的异常周转率可能参与了 DN 的发病机制。

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