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GRP78/BiP 是否是类风湿关节炎患者潜在的唾液生物标志物?

Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

机构信息

Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy.

出版信息

Proteomics Clin Appl. 2010 Mar;4(3):315-24. doi: 10.1002/prca.200900082. Epub 2010 Jan 4.

Abstract

PURPOSE

In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva.

EXPERIMENTAL DESIGN

We combined 2-DE and MS to analyze the whole saliva protein profile of 20 RA patients in comparison with 20 sex- and age-matched healthy subjects.

RESULTS

Eight salivary proteins resulted differentially expressed, namely calgranulin A, calgranulin B, apolipoprotein A-1, 6-phosphogluconate dehydrogenase, peroxiredoxin 5, epidermal fatty acid-binding protein, 78 kDa glucose-regulated protein precursor (GRP78/BiP), and 14-3-3 proteins. It is particularly interesting that chaperone GRP78/BiP showed the greatest increase in RA patients. This finding was validated by Western Blot analysis and the over-expression of GRP78/BiP appear to be distinctive of RA and drugs treatment independent.

CONCLUSIONS AND CLINICAL RELEVANCE

This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.

摘要

目的

在过去的几年中,人们广泛地分析了血清和关节滑液中的蛋白质组学,以寻找类风湿关节炎(RA)生物标志物。然而,迄今为止,尚未有研究调查这种情况下的唾液生物标志物。因此,本研究旨在探讨人类全唾液中 RA 潜在生物标志物的存在。

实验设计

我们将 2-DE 和 MS 相结合,分析了 20 名 RA 患者和 20 名性别和年龄匹配的健康对照者的全唾液蛋白谱。

结果

有 8 种唾液蛋白表达差异,分别为钙粒蛋白 A、钙粒蛋白 B、载脂蛋白 A-1、6-磷酸葡萄糖酸脱氢酶、过氧化物酶 5、表皮脂肪酸结合蛋白、78 kDa 葡萄糖调节蛋白前体(GRP78/BiP)和 14-3-3 蛋白。特别有趣的是,伴侣蛋白 GRP78/BiP 在 RA 患者中表达增加最大。Western Blot 分析验证了这一发现,并且 GRP78/BiP 的过度表达似乎是 RA 的特征,与药物治疗无关。

结论和临床相关性

本研究为进一步评估 GRP78/BiP 与疾病不同临床/血清学方面之间的任何相关性提供了依据,以便改进 RA 的诊断算法。

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