دورية أكاديمية
PLOS ONE / Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes
| العنوان: | PLOS ONE / Orthologous proteins of experimental de- and remyelination are differentially regulated in the CSF proteome of multiple sclerosis subtypes |
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| المؤلفون: | Illes, Zsolt, Lassmann, Hans, Martin, Nellie A., Nawrocki, Arkadiusz, Molnar, Viktor, Elkjaer, Maria L., Thygesen, Eva K., Palkovits, Miklos, Acs, Peter, Sejbaek, Tobias |
| بيانات النشر: | PLoS |
| سنة النشر: | 2018 |
| المجموعة: | MedUni Vienna ePub (Medzinische Universität Wien) |
| مصطلحات موضوعية: | Multiple sclerosis, Cerebrospinal fluid, Gene expression, Proteomes, Inflammation, Gene regulation, Microglial cells, Transcriptome analysis |
| جغرافية الموضوع: | UMW:14527 |
| الوصف: | 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text/html |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | vignette : https://repositorium.meduniwien.ac.at/titlepage/urn/urn:nbn:at:at-ubmuw:3-42824/128Test; urn:nbn:at:at-ubmuw:3-42824; https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-42824Test; local:99146054513703331; system:AC16208098 |
| DOI: | 10.1371/journal.pone.0202530 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0202530Test https://resolver.obvsg.at/urn:nbn:at:at-ubmuw:3-42824Test |
| حقوق: | cc-by_4 |
| رقم الانضمام: | edsbas.154152CA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0202530 |