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http://hdl.handle.net/1942/22468
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DC Field | Value | Language |
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dc.contributor.advisor | HENDRIX, Sven | - |
dc.contributor.advisor | GOU FABREGAS, Myriam | - |
dc.contributor.author | Mampay, Myrthe | - |
dc.date.accessioned | 2016-09-29T18:00:18Z | - |
dc.date.available | 2016-09-29T18:00:18Z | - |
dc.date.issued | 2016 | - |
dc.identifier.uri | http://hdl.handle.net/1942/22468 | - |
dc.description.abstract | A disintegrin and metalloproteinase 17 (ADAM17) is responsible for shedding inflammatory mediators, such as TNF- and the phagocytic receptor CD36. Therefore, we hypothesize that inhibition of ADAM17 limits the production of pro-inflammatory cytokines and improves macrophage clearance of damaged tissue, leading to a better functional recovery after SCI.T-cut hemisection SCI was performed on ADAM17 hypomorphic (ADAM17ex/ex) and ADAM17 macrophage-specific knockout (ADAM17 M-KO) mice. Bone marrow-derived macrophages (BMDMs) were isolated from ADAM17ex/ex and ADAM17-overexpressing lentiviral particles were used to restore ADAM17 expression. ADAM17ex/ex mice showed an improved functional recovery after SCI and ADAM17ex/ex BMDMs produce reduced levels of sTNF-. Lentiviral-mediated overexpression of ADAM17 rescued the shedding of TNF- in ADAM17ex/ex BMDMs. ADAM17ex/ex macrophages show increased phagocytosis of spinal cord debris in vitro. However, no improvement in functional recovery was observed in ADAM17 M-KO mice compared to controls. These data indicate that ADAM17 affects functional recovery after SCI. Although ADAM17 limits BMDM phagocytic activity and stimulates sTNF- production, the observed improved functional recovery in ADAM17ex/ex mice was absent in ADAM17 M-KO mice. These results imply that the effect of ADAM17 in other phagocytic cell types, including microglia, are encouraged as they represent a promising therapeutic target to improve functional outcome after SCI. | - |
dc.format.mimetype | Application/pdf | - |
dc.language | nl | - |
dc.publisher | tUL | - |
dc.title | A disintegrin and metalloproteinase 17 (ADAM17): an important factor to improve regeneration after CNS trauma | - |
dc.type | Theses and Dissertations | - |
local.bibliographicCitation.jcat | T2 | - |
dc.description.notes | master in de biomedische wetenschappen-klinische moleculaire wetenschappen | - |
local.type.specified | Master thesis | - |
item.contributor | Mampay, Myrthe | - |
item.accessRights | Open Access | - |
item.fullcitation | Mampay, Myrthe (2016) A disintegrin and metalloproteinase 17 (ADAM17): an important factor to improve regeneration after CNS trauma. | - |
item.fulltext | With Fulltext | - |
Appears in Collections: | Master theses |
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File | Description | Size | Format | |
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10303022015249.pdf | 35.1 MB | Adobe PDF | View/Open |
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