Wang Xia, Hao Qiang, Zhao Yuanli, Guo Yi, Ge Wei
National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
Proteomics Clin Appl. 2017 May;11(5-6). doi: 10.1002/prca.201600093. Epub 2017 Feb 13.
Detailed 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.
This 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.
Our 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.
Cell-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.
脑动静脉畸形（bAVM）潜在的详细而确切的机制在临床上仍令人困惑。了解蛋白质和信号通路的定量变化将为临床医生理解bAVM的形成和发展提供有用信息，从而指导个体化治疗策略。本研究旨在使用串联质量标签标记建立一个大型人类bAVM蛋白质组数据库，并检测人类bAVM中蛋白质表达和信号通路的变化。
本研究使用定量6重串联质量标签标记来分析bAVM病变中的蛋白质变化。采用综合生物信息学分析对改变的蛋白质和相关信号通路进行分类和鉴定。蛋白质印迹分析用于验证蛋白质组学数据。
我们的工作建立了迄今为止第一个人类bAVM蛋白质组数据库。共鉴定出1264种蛋白质，其中316种蛋白质的表达有显著差异，249种蛋白质上调。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。发现代表细胞间相互作用重要领域的三条信号通路（粘着斑、紧密连接和缝隙连接）在bAVM中被激活。蛋白质组学数据可通过ProteomeXchange获得，标识符为PXD003289。
细胞间相互作用，包括粘着斑、紧密连接和缝隙连接，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信息，指导可能的精确和个体化治疗策略。
