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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/22468

Title: A disintegrin and metalloproteinase 17 (ADAM17): an important factor to improve regeneration after CNS trauma
Authors: Mampay, Myrthe
Advisors: HENDRIX, Sven
Issue Date: 2016
Publisher: tUL
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.
Notes: master in de biomedische wetenschappen-klinische moleculaire wetenschappen
URI: http://hdl.handle.net/1942/22468
Category: T2
Type: Theses and Dissertations
Appears in Collections: Master theses

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