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http://hdl.handle.net/1942/30888
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DC Field | Value | Language |
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dc.contributor.author | HOUBEN, Evelien | - |
dc.contributor.author | JANSSENS, Kris | - |
dc.contributor.author | HERMANS, Doryssa | - |
dc.contributor.author | Vandooren, Jennifer | - |
dc.contributor.author | Van den Haute, Chris | - |
dc.contributor.author | SCHEPERS, Melissa | - |
dc.contributor.author | VANMIERLO, Tim | - |
dc.contributor.author | LAMBRICHTS, Ivo | - |
dc.contributor.author | VAN HORSSEN, Jack | - |
dc.contributor.author | Baekelandt, Veerle | - |
dc.contributor.author | OPDENAKKER, Ghislain | - |
dc.contributor.author | Baron, Wia | - |
dc.contributor.author | BROUX, Bieke | - |
dc.contributor.author | Slaets, Helena | - |
dc.contributor.author | HELLINGS, Niels | - |
dc.date.accessioned | 2020-03-30T13:17:07Z | - |
dc.date.available | 2020-03-30T13:17:07Z | - |
dc.date.issued | 2020 | - |
dc.date.submitted | 2020-03-30T12:03:57Z | - |
dc.identifier.citation | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF, AMERICA, 117 (9) , p. 5028 -5038 | - |
dc.identifier.uri | http://hdl.handle.net/1942/30888 | - |
dc.description.abstract | The brain's endogenous capacity to restore damaged myelin deteriorates during the course of demyelinating disorders. Currently, no treatment options are available to establish remyelination. Chronic demyelination leads to damaged axons and irreversible destruction of the central nervous system (CNS). We identified two promising therapeutic candidates which enhance remyelination: oncostatin M (OSM), a member of the interleukin-6 family, and downstream mediator tissue inhibitor of metalloproteinases-1 (TIMP-1). While remyelination was completely abrogated in OSMR beta knockout (KO) mice, OSM overexpression in the chronically demyelinated CNS established remyelination. Astrocytic TIMP-1 was demonstrated to play a pivotal role in OSM-mediated remyelination. Astrocyte-derived TIMP-1 drove differentiation of oligodendrocyte precursor cells into mature oligodendrocytes in vitro. In vivo, TIMP-1 deficiency completely abolished spontaneous remyelination, phenocopying OSMR beta KO mice. Finally, TIMP-1 was expressed by human astrocytes in demyelinated multiple sclerosis lesions, confirming the human value of our findings. Taken together, OSM and its downstream mediator TIMP-1 have the therapeutic potential to boost remyelination in demyelinating disorders. | - |
dc.description.sponsorship | We thank Dr. Tom Struys, Katrien Wauterickx, and Joke Vanhoof for excellent technical assistance. This work was financially supported by grants from the Research Foundation of Flanders (FWO Vlaanderen, G04441N, G050617N, G0A5716N, and 1106817N), the Interuniversity Attraction Poles (IUAP-P7-39), the Belgian MS-Liga and the Charcot Foundation of Belgium, Methusalem NEURONET, the European FP7 project, HEALTH-F2-2011-278850 (INMiND), and Bijzonder Onderzoeksfonds (BOF)-UHasselt. | - |
dc.language.iso | en | - |
dc.publisher | NATL ACAD SCIENCES | - |
dc.rights | 2020 National Academy of Sciences. | - |
dc.subject.other | oncostatin M | - |
dc.subject.other | remyelination | - |
dc.subject.other | oligodendrocyte precursor cells | - |
dc.subject.other | astrocytes | - |
dc.subject.other | tissue inhibitor of metalloproteinases-1 | - |
dc.title | Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 5038 | - |
dc.identifier.issue | 9 | - |
dc.identifier.spage | 5028 | - |
dc.identifier.volume | 117 | - |
local.format.pages | 11 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Hellings, N (reprint author), Hasselt Univ, Biomed Res Inst, Dept Immunol, B-3590 Diepenbeek, Belgium. | - |
dc.description.notes | niels.hellings@uhasselt.be | - |
dc.description.other | Hellings, N (reprint author), Hasselt Univ, Biomed Res Inst, Dept Immunol, B-3590 Diepenbeek, Belgium. niels.hellings@uhasselt.be | - |
local.publisher.place | 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.source.type | Article | - |
dc.identifier.doi | 10.1073/pnas.1912910117 | - |
dc.identifier.pmid | 32071226 | - |
dc.identifier.isi | WOS:000518473500077 | - |
dc.contributor.orcid | Vandooren, Jennifer/0000-0002-7157-3370; Lambrichts, | - |
dc.contributor.orcid | Ivo/0000-0001-7520-0021; Opdenakker, Ghislain/0000-0003-1714-2294 | - |
dc.identifier.eissn | 1091-6490 | - |
local.provider.type | wosris | - |
local.uhasselt.uhpub | yes | - |
item.validation | ecoom 2021 | - |
item.contributor | HOUBEN, Evelien | - |
item.contributor | JANSSENS, Kris | - |
item.contributor | HERMANS, Doryssa | - |
item.contributor | Vandooren, Jennifer | - |
item.contributor | Van den Haute, Chris | - |
item.contributor | SCHEPERS, Melissa | - |
item.contributor | VANMIERLO, Tim | - |
item.contributor | LAMBRICHTS, Ivo | - |
item.contributor | VAN HORSSEN, Jack | - |
item.contributor | Baekelandt, Veerle | - |
item.contributor | OPDENAKKER, Ghislain | - |
item.contributor | Baron, Wia | - |
item.contributor | BROUX, Bieke | - |
item.contributor | Slaets, Helena | - |
item.contributor | HELLINGS, Niels | - |
item.accessRights | Open Access | - |
item.fullcitation | HOUBEN, Evelien; JANSSENS, Kris; HERMANS, Doryssa; Vandooren, Jennifer; Van den Haute, Chris; SCHEPERS, Melissa; VANMIERLO, Tim; LAMBRICHTS, Ivo; VAN HORSSEN, Jack; Baekelandt, Veerle; OPDENAKKER, Ghislain; Baron, Wia; BROUX, Bieke; Slaets, Helena & HELLINGS, Niels (2020) Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinases-1 drives remyelination. In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF, AMERICA, 117 (9) , p. 5028 -5038. | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0027-8424 | - |
crisitem.journal.eissn | 1091-6490 | - |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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2020 Houben et al PNAS suppl.pdf | Published version | 827.28 kB | Adobe PDF | View/Open |
2020 Houben et al PNAS.pdf | Published version | 3.17 MB | Adobe PDF | View/Open |
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