title: Dysregulation of cell-cell interactions in brain arteriovenous malformations: A quantitative proteomic study.
abstract: 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.
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China.
authors.forename: Yuanli
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Tsinghua Changgung Hospital, Beijing, 102218, China.|Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, 071000, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002450:Cell Communication; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics; D055815:Young Adult
keywords: Brain arteriovenous malformations; Cell-cell interaction; Quantitative proteomics; Tandem mass tag labeling