Dysregulation of Cell-Cell Interaction in Brain Arteriovenous Malformations: A Quantitative Proteomics Study

ABSTRACT: Object. Detailed and exact mechanisms underlying brain arteriovenous malformations (bAVM) are still confusing in clinic. Understanding the quantitative changes of proteins and signaling pathways would provide useful information for clinicians to understand the formation and development of bAVM and therefore give proper individual treatment strategies. This study was performed to establish a huge human bAVM proteome database by tandem mass tag (TMT)-labeling technique and detect the alteration of proteins and pathways in the development of human bAVM. Methods. This study used quantitative proteomics to profile protein changes with the 6-plex TMT labeling in bAVM lesions. Integrated bioinformatics analysis were used to classify and identify the altered proteins and relating signaling pathways. Western blot analyses were used to identify the reliability of the proteomic data. Results. Our work established one of the largest human bAVM proteome databases to date. A total of 1264 proteins were identified, among which the expression of 316 proteins were changed with 249 proteins upregulated. Bioinformatics analysis revealed a close relevance between cell-cell interactions including focal adhesion, tight junction, gap junction and the development of bAVM. Conclusions. Cell-cell interactions, including focal adhesion, tight junction and gap junction played vital roles in the formation and development of bAVM. Understanding the molecular mechanism underlying bAVM is important for the development of future therapeutic approaches, thereafter making precise and individual treatment strategies in clinic.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Wei Ge  

LAB HEAD: Wei Ge

PROVIDER: PXD003289 | Pride | 2017-01-20

REPOSITORIES: Pride