Show simple item record Martin, NA Nawrocki, A Molnar, V Elkjaer, ML Thygesen, EK Palkovits, M Acs, P Sejbaek, T Nielsen, HH Hegedus, Z Sellebjerg, F Molnar, T Barbosa, EGV Alcaraz, N Gallyas, F Jr Svenningsen, AF Baumbach, J Lassmann, H Larsen, MR Illes, Z 2019-11-21T13:16:22Z 2019-11-21T13:16:22Z 2018
dc.identifier 85053547403
dc.identifier.citation journalVolume=13;journalIssueNumber=8;journalTitle=PLOS ONE;pagerange=Paper. e0202530;journalAbbreviatedTitle=PLOS ONE;
dc.identifier.uri doi:10.1371/journal.pone.0202530
dc.description.abstract OBJECTIVE: Here, we applied a multi-omics approach (i) to examine molecular pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and (ii) to translate these findings to the CSF proteome in order to identify molecules that are differentially expressed among MS subtypes. METHODS: To relate differentially expressed genes in MS lesions to de- and remyelination, we compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced de- and remyelination. Protein products of the overlapping orthologous genes were measured within the CSF by quantitative proteomics, parallel reaction monitoring (PRM). Differentially regulated proteins were correlated with molecular markers of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of differentially regulated orthologous genes and proteins were examined in the CPZ model. RESULTS: In the demyelinated and remyelinated corpus callosum, we detected 1239 differentially expressed genes; 91 orthologues were also differentially expressed in MS lesions. Pathway analysis of these orthologues suggested that the TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit PSMB9 were related to de- and remyelination. We designed 129 peptides representing 51 orthologous proteins, measured them by PRM in 97 individual CSF, and compared their levels between relapsing (n = 40) and progressive MS (n = 57). Four proteins were differentially regulated among relapsing and progressive MS: tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2), and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2 showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26. CONCLUSIONS: Pathology-based multi-omics identified four CSF markers that were differentially expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in relapsing MS were associated with reduced inflammation and reflected reparatory processes, in contrast to the upregulated orthologue APOC2 in progressive MS that reflected changes in lipid metabolism associated with increased inflammation.
dc.title Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes
dc.type Journal Article 2019-07-30T07:15:29Z
dc.language.rfc3066 en
dc.rights.holder NULL
dc.identifier.mtmt 3407190
dc.identifier.wos 000441850400083
dc.identifier.pubmed 30114292
dc.contributor.institution Aneszteziológiai és Intenzív Terápiás Intézet
dc.contributor.institution Szentágothai János Kutatóközpont
dc.contributor.institution Biokémiai és Orvosi Kémiai Intézet
dc.contributor.institution Biofizikai Intézet
dc.contributor.institution Genetikai Intézet
dc.contributor.institution MTA-PTE Nukleáris-Mitokondriális Interakciók Kutatócsoport
dc.contributor.institution Anatómiai, Szövet- és Fejlődéstani Intézet
dc.contributor.institution Anatómiai, Szövet- és Fejlődéstani Intézet
dc.contributor.institution Humán Agyminta Bank
dc.contributor.institution Humán Agyminta Bank
dc.contributor.institution MTA-SE Neuromorfológiai és Neuroendokrin Kutatócsoport (2006-ig: MTA-SE Neuroendokrin Kutatócsoport)
dc.contributor.institution MTA-SE Neuromorfológiai Kutatócsoport (2007-től beolvadt az SE04-be)
dc.contributor.institution Központi Laboratóriumok
dc.contributor.institution MTA Kísérleti Orvostudományi Kutatóintézet
dc.contributor.institution Neurológiai Klinika
dc.contributor.institution Egészségtudományi Doktori Iskola
dc.contributor.institution MTA-PTE Klinikai Idegtudományi Képalkotó Kutatócsoport
dc.contributor.institution Genomikai Medicina és Ritka Betegségek Intézete

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