Proteome Analysis of Urinary Biomarkers in a Bovine IRBP-Induced Uveitis Rat Model via Data-Independent Acquisition and Parallel Reaction Monitoring Proteomics.
Proteome Analysis of Urinary Biomarkers in a Bovine IRBP-Induced Uveitis Rat Model via Data-Independent Acquisition and Parallel Reaction Monitoring Proteomics.
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通过数据独立采集和平行反应监测蛋白质组学对牛IRBP诱导的葡萄膜炎大鼠模型中尿生物标志物的蛋白质组学分析。
DOI：
10.3389/fmolb.2022.831632
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发表时间：
2022
影响因子：
5
通讯作者：
Gao Y
中科院分区：
文献类型：
--
作者：
Qin W;Qin X;Li L;Gao Y
葡萄膜炎是一组眼内炎症性疾病，是造成劳动年龄人口严重视力损害的主要原因之一。本研究旨在基于蛋白质组分析筛选潜在的葡萄膜炎尿液生物标志物。采用牛光间受体类视黄酸结合蛋白（IRBP）诱导的实验性自身免疫性葡萄膜炎（EAU）大鼠模型模拟葡萄膜炎。在发现阶段，通过数据独立获取（DIA）蛋白质组学技术共鉴定出704种尿蛋白，其中76种蛋白发生了显著变化（分别在牛IRBP免疫后第5、8和12天发生了34、36和37种）。差异蛋白的基因本体注释表明，急性期反应、先天免疫反应、中性粒细胞聚集和慢性炎症反应显著富集。蛋白-蛋白相互作用网络表明，这些差异尿蛋白在EAU中作为一个群体具有生物学联系。在验证阶段，通过平行反应监测（PRM）靶向定量分析，验证了17种具有人类同源物的蛋白作为葡萄膜炎相关的潜在标志物。即使在没有临床表现或组织病理损伤的情况下，仍有12种差异蛋白发生改变。这12种蛋白是早期诊断葡萄膜炎的潜在生物标志物，可以预防视力障碍的发展。5种差异蛋白在3个时间点发生变化，并随着葡萄膜炎的进展呈现进行性变化，另外5种差异蛋白仅在第12天EAU严重程度达到高峰时发生变化。这10种蛋白可作为葡萄膜炎预后评价的潜在生物标志物。我们的研究结果表明，尿蛋白组可以灵敏地反映EAU的动态病理生理变化，并代表了将尿蛋白生物标志物应用于葡萄膜炎的第一步。
Uveitis, a group of intraocular inflammatory diseases, is one of the major causes of severe visual impairment among the working-age population. This study aimed to screen potential urinary biomarkers for uveitis based on proteome analysis. An experimental autoimmune uveitis (EAU) rat model induced by bovine interphotoreceptor retinoid-binding protein (IRBP) was used to mimic uveitis. In discovery phase, a total of 704 urinary proteins were identified via data-independent acquisition (DIA) proteomic technique, of which 76 were significantly changed (34, 36, and 37 on days 5, 8, and 12, respectively, after bovine IRBP immunization). Gene Ontology annotation of the differential proteins indicates that acute-phase response, innate immune response, neutrophil aggregation, and chronic inflammatory response were significantly enriched. Protein-protein interaction network indicates that these differential urinary proteins were biologically connected in EAU, as a group. In validation phase, 17 proteins having human orthologs were verified as the potential markers associated with uveitis by parallel reaction monitoring (PRM) targeted quantitative analysis. Twelve differential proteins changed even when there were no clinical manifestations or histopathological ocular damage. These 12 proteins are potential biomarkers for early diagnosis of uveitis to prevent the development of visual impairment. Five differential proteins changed at three time-points and showed progressive changes as the uveitis progressed, and another five differential proteins changed only on day 12 when EAU severity peaked. These 10 proteins may serve as potential biomarkers for prognostic evaluation of uveitis. Our findings revealed that the urinary proteome could sensitively reflect dynamic pathophysiological changes in EAU, and represent the first step towards the application of urinary protein biomarkers for uveitis.
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影响因子：
4.6
作者：
Fujita K;Kume H;Matsuzaki K;Kawashima A;Ujike T;Nagahara A;Uemura M;Miyagawa Y;Tomonaga T;Nonomura N
通讯作者：
Nonomura N
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
7.3
作者：
Bauer D;Kasper M;Walscheid K;Koch JM;Müther PS;Kirchhof B;Heiligenhaus A;Heinz C
通讯作者：
Heinz C
DOI：
10.3390/molecules26071991
发表时间：
2021-04-01
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Benabdelkamel H;Masood A;Ekhzaimy AA;Alfadda AA
通讯作者：
Alfadda AA
影响因子：
3.4
作者：
LEHNER, T;ADINOLFI, M
通讯作者：
ADINOLFI, M