Tandem mass tag-based serum proteomic profiling revealed diabetic foot ulcer pathogenesis and potential therapeutic targets.
Tandem mass tag-based serum proteomic profiling revealed diabetic foot ulcer pathogenesis and potential therapeutic targets.
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基于串联质量标签的血清蛋白质组学分析揭示了糖尿病足溃疡的发病机制和潜在的治疗靶点
DOI：
10.1080/21655979.2022.2027173
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发表时间：
2022-03
期刊：
影响因子：
4.9
通讯作者：
Guo F
中科院分区：
文献类型：
--
作者：
Yu XT;Wang F;Ding JT;Cai B;Xing JJ;Guo GH;Guo F
摘要糖尿病足溃疡（DFU）是糖尿病最严重的并发症之一，与高截肢率和生活质量下降有关。血清蛋白在DFU发生发展中的作用引起了人们的广泛关注。在这项研究中，我们的目的是定义和比较DFU患者和健康对照（HC）的血清蛋白质组，为DFU的发病机制提供新的见解。DFU患者和年龄和性别匹配的HC入组本研究（n = 54）。采用基于液相色谱-质谱（LC-MS/MS）定量蛋白质组学的串联质量标签（TMT）方法筛选DFU患者和HC血清蛋白质的变化，并通过平行反应监测（PRM）和酶联免疫吸附试验（ELISA）进一步验证差异表达蛋白（DEPs）。DFU组和HC组共检测到173个DEPs（100个上调，73个下调）（P < 0.05）。蛋白质组学和生物信息学分析表明，DFU组中的蛋白质主要与细胞外基质（ECM）-受体相互作用以及补体和凝血级联反应有关。通过PRM和ELISA进一步验证了上调的DEPs。DFU中LRG 1、CD 5L、CRP、IGHA 1和LBP表达上调，这些蛋白主要与免疫应答和补体激活有关。我们的研究结果有助于更全面地了解DFU的发病机制，并对潜在的治疗靶点提供新的见解。
ABSTRACT Diabetic foot ulcer (DFU), one of the most serious complications of diabetes mellitus, is associated with a high amputation rate and decreased life quality. The impact of blood serum proteins on the occurrence and development of DFU has attracted a lot of interest. In this study, we aimed to define and compare the serum proteome of patients with DFU and healthy control (HC) to provide new insights into DFU pathogenesis. DFU patients and age- and sex-matched HCs were enrolled in this study (n = 54). We screened alterations in blood serum proteins from DFU patients and HC using a tandem mass tag (TMT) method based on liquid chromatography-mass spectrometry (LC-MS/MS) quantitative proteomics, and the differentially expressed proteins (DEPs) were further validated by parallel reaction monitoring (PRM) and enzyme-linked immunosorbent assay (ELISA). A total of 173 DEPs (100 up-regulated and 73 down-regulated) were identified between the DFU and HC groups (P < 0.05). Proteomic and bioinformatics analyses indicated that the proteins in the DFU group were mainly related to extracellular matrix (ECM)-receptor interaction and complement and coagulation cascades. The up-regulated DEPs were further verified by PRM and ELISA. LRG1, CD5L, CRP, IGHA1, and LBP were proved upregulated in DFU and these proteins are mainly related to immune response and complement activation. Our findings help to provide a more comprehensive understanding of the pathogenesis of DFU and new insight into potential therapeutic targets.
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影响因子：
9.8
作者：
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通讯作者：
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作者：
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