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http://hdl.handle.net/1942/21569
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DC Field | Value | Language |
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dc.contributor.author | VANGANSEWINKEL, Tim | - |
dc.contributor.author | GEURTS, Nathalie | - |
dc.contributor.author | Quanten, Kirsten | - |
dc.contributor.author | NELISSEN, Sofie | - |
dc.contributor.author | LEMMENS, Stefanie | - |
dc.contributor.author | GEBOES, Lies | - |
dc.contributor.author | DOOLEY, Dearbhaile | - |
dc.contributor.author | VIDAL VERA, Pia | - |
dc.contributor.author | Pejler, Gunnar | - |
dc.contributor.author | HENDRIX, Sven | - |
dc.date.accessioned | 2016-06-28T13:43:20Z | - |
dc.date.available | 2016-06-28T13:43:20Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | FASEB JOURNAL, 30 (5), p. 2040-2057 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.uri | http://hdl.handle.net/1942/21569 | - |
dc.description.abstract | An important barrier for axon regeneration and recovery after traumatic spinal cord injury (SCI) is attributed to the scar that is formed at the lesion site. Here, we investigated the effect of mouse mast cell protease (mMCP) 6, a mast cell (MC)-specific tryptase, on scarring and functional recovery after a spinal cord hemisection injury. Functional recovery was significantly impaired in both MC-deficient and mMCP6-knockout (mMCP6(-/-)) mice after SCI compared with wild-type control mice. This decrease in locomotor performance was associated with an increased lesion size and excessive scarring at the injury site. Axon growth-inhibitory chondroitin sulfate proteoglycans and the extracellular matrix components fibronectin, laminin, and collagen IV were significantly up-regulated in MC-deficient and mMCP6(-/-) mice, with an increase in scar volume between 23 and 32%. A degradation assay revealed that mMCP6 directly cleaves fibronectin and collagen IV in vitro. In addition, gene expression levels of the scar components fibronectin, aggrecan, and collagen IV were increased up to 6.8-fold in mMCP6(-/-) mice in the subacute phase after injury. These data indicate that endogenous mMCP6 has scar-suppressing properties after SCI via indirect cleavage of axon growth-inhibitory scar components and alteration of the gene expression profile of these factors.-Vangansewinkel, T., Geurts, N., Quanten, K., Nelissen, S., Lemmens, S., Geboes, L., Dooley, D., Vidal, P. M., Pejler, G., Hendrix, S. Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6. www.fasebj.org | - |
dc.description.sponsorship | The authors thank Dr. David Lee (Novartis Pharma, Basel, Switzerland) and Dr. Peter Nigrovic (Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA) for providing the mMCP6-/- mice, and Dr. Leen Timmermans (Hasselt University) for her help with the qPCR analysis and immunohistochemistry. This study was supported in part by grants from Deutsche Forschungsgemeinschaft (SPP1394), Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO; G.0389.12, G0A5813, G.0834.11N, and G0A58113 to S.H., and 1.2.917.14N to N.G.), and from Agentschap voor Innovatie door Wetenschap en Technologie (101517 to T.V.). This work has also benefited from the support of the COST Action BM1007 Mast Cells and Basophils-Targets for Innovative Therapies. | - |
dc.language.iso | en | - |
dc.publisher | FEDERATION AMER SOC EXP BIOL | - |
dc.rights | © FASEB | - |
dc.subject.other | CNS trauma; mMCP6; ECM remodeling; gene expression; improved outcome | - |
dc.subject.other | CNS trauma; mMCP6; ECM remodeling; gene expression; improved outcome | - |
dc.title | Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6 | - |
dc.type | Journal Contribution | - |
dc.identifier.epage | 2057 | - |
dc.identifier.issue | 5 | - |
dc.identifier.spage | 2040 | - |
dc.identifier.volume | 30 | - |
local.format.pages | 18 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | [Vangansewinkel, Tim; Geurts, Nathalie; Quanten, Kirsten; Nelissen, Sofie; Lemmens, Stefanie; Geboes, Lies; Dooley, Dearbhaile; Vidal, Pia M.; Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Dept Morphol, Diepenbeek, Belgium. [Pejler, Gunnar] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden. [Pejler, Gunnar] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden. [Vidal, Pia M.] Univ Hlth Network, Div Genet & Dev, Krembil Neurosci Ctr, Toronto, ON, Canada. | - |
local.publisher.place | BETHESDA | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
dc.identifier.doi | 10.1096/fj.201500114R | - |
dc.identifier.isi | 000374879400030 | - |
item.contributor | VANGANSEWINKEL, Tim | - |
item.contributor | GEURTS, Nathalie | - |
item.contributor | Quanten, Kirsten | - |
item.contributor | NELISSEN, Sofie | - |
item.contributor | LEMMENS, Stefanie | - |
item.contributor | GEBOES, Lies | - |
item.contributor | DOOLEY, Dearbhaile | - |
item.contributor | VIDAL VERA, Pia | - |
item.contributor | Pejler, Gunnar | - |
item.contributor | HENDRIX, Sven | - |
item.validation | ecoom 2017 | - |
item.fullcitation | VANGANSEWINKEL, Tim; GEURTS, Nathalie; Quanten, Kirsten; NELISSEN, Sofie; LEMMENS, Stefanie; GEBOES, Lies; DOOLEY, Dearbhaile; VIDAL VERA, Pia; Pejler, Gunnar & HENDRIX, Sven (2016) Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6. In: FASEB JOURNAL, 30 (5), p. 2040-2057. | - |
item.accessRights | Restricted Access | - |
item.fulltext | With Fulltext | - |
crisitem.journal.issn | 0892-6638 | - |
crisitem.journal.eissn | 1530-6860 | - |
Appears in Collections: | PhD theses Research publications |
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vangansewinkel2016.pdf Restricted Access | Published version | 2.15 MB | Adobe PDF | View/Open Request a copy |
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