Dysregulation of cell-cell interactions in brain arteriovenous malformations: A quantitative proteomic study
Dysregulation of cell-cell interactions in brain arteriovenous malformations: A quantitative proteomic study
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脑动静脉畸形中细胞间相互作用的失调：定量蛋白质组学研究
DOI：
10.1002/prca.201600093
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发表时间：
2017
影响因子：
2
通讯作者：
Ge Wei
中科院分区：
文献类型：
--
作者：
Wang Xia;Hao Qiang;Zhao Yuanli;Guo Yi;Ge Wei
目的脑动静脉畸形（bAVM）的详细和确切的发病机制在临床上仍然是个谜.了解bAVM的蛋白质和信号通路的定量变化，将为临床医生了解bAVM的形成和发展提供有用的信息，指导个体化治疗策略。本研究旨在建立一个大型的人类bAVM蛋白质组数据库，并利用串联mass tag标记技术检测bAVM病变中蛋白质表达和通路的变化。实验设计本研究采用定量6重串联mass tag标记技术分析bAVM病变中蛋白质的变化。综合生物信息学分析，分类和鉴定改变的蛋白质和相关的信号通路。Western blot分析被用来验证蛋白质组data.ResultsWe的工作建立了迄今为止的第一个人类bAVM蛋白质组数据库。共鉴定了1264个蛋白质，其中316个蛋白质表达显著差异，249个蛋白质表达上调。生物信息学分析表明，改变的蛋白质具有密切的功能相关性，包括整合素细胞表面相互作用，细胞外基质组织和平滑肌收缩。三种信号通路（粘着斑、紧密连接和间隙连接）是细胞间相互作用的重要竞技场，在bAVM中被激活。蛋白质组学数据可通过ProteomeXchange获得，标识符为PXD 003289。结论和临床意义细胞间相互作用，包括粘着斑、紧密连接和间隙连接，在人类bAVM中受到显著影响。了解bAVM的分子机制将为未来治疗方法的开发提供有用的信息，指导可能的精确和个性化治疗策略。
PurposeDetailed and exact mechanisms underlying brain arteriovenous malformations (bAVM) are still clinically confusing. Understanding the quantitative changes in proteins and signaling pathways would provide useful information for clinicians to understand the formation and development of bAVM, guiding individualized treatment strategies. This study was performed to establish a large human bAVM proteome database using tandem mass tag labeling and to detect changes of protein expression and pathways in human bAVM.Experimental designThis study used quantitative 6‐plex tandem mass tag labeling to profile protein changes in bAVM lesions. Integrated bioinformatics analysis was used to classify and identify the altered proteins and relating signaling pathways. Western blot analyzes were used to validate the proteomic data.ResultsOur work established the first human bAVM proteome databases to date. A total of 1264 proteins were identified, and the expression of 316 proteins was significantly differentially expressed, with 249 upregulated proteins. Bioinformatics analysis demonstrated that the altered proteins had close functional correlations, including integrin cell surface interactions, extracellular matrix organization, and smooth muscle contraction. Three signaling pathways (focal adhesions, tight junctions, and gap junctions), which represent an important arena of cell–cell interactions, were found to be activated in bAVM. The proteomics data are available via ProteomeXchange with identifier PXD003289.Conclusion and clinical relevanceCell–cell interactions, including focal adhesions, tight junctions, and gap junctions, were significantly influenced in human bAVM. Understanding the molecular mechanisms that underlie bAVM would provide useful information for the development of future therapeutic approaches, guiding possible precise and individual treatment strategies.