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Characterisation of extracellular vesicle-subsets derived from brain endothelial
cells and analysis of their protein cargo modulation after TNF exposure
#MMPMID28473883
Dozio V
; Sanchez JC
J Extracell Vesicles
2017[]; 6
(1
): 1302705
PMID28473883
show ga
Little is known about the composition and functional differences between
extracellular vesicle (EV) subsets, such as microvesicles (MVs) and exosomes
(EXOs), nor to what extent their cargo reflects the phenotypic state of the cell
of origin. Brain endothelial cells are the constitutive part of the blood-brain
barrier (BBB), a selective barrier that maintains brain homeostasis. BBB
impairment is associated with several neuroinflammatory diseases with the
pro-inflammatory cytokine tumour necrosis factor (TNF) often playing a key role.
In the present study, shotgun proteomics and parallel reaction monitoring
(PRM)-based targeted mass spectrometry were used to characterise brain
endothelial cell-released EVs, and to study how TNF exposure modulated EV protein
cargoes. MVs were found to be enriched in mitochondrial and cytoskeletal
proteins, whereas EXOs were enriched in adhesion, histone and ribosomal proteins.
After stimulation with TNF, several proteins involved in TNF and NF-?B signalling
pathways, that were found to be differentially expressed in cells, were also
differentially expressed in both MVs and EXOs. Thus, our results revealed some
novel proteins as potentially useful candidates for discriminating between MVs
and EXOs, together with additional evidence that cells "package" proteins in EVs
systematically and according to their phenotypic state.
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