title: Mast cells promote scar remodeling and functional recovery after spinal cord injury via mouse mast cell protease 6.
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.
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Tim
authors.initials: T
authors.lastname: Vangansewinkel
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Geurts
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Kirsten
authors.initials: K
authors.lastname: Quanten
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Sofie
authors.initials: S
authors.lastname: Nelissen
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Stefanie
authors.initials: S
authors.lastname: Lemmens
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Lies
authors.initials: L
authors.lastname: Geboes
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Dearbhaile
authors.initials: D
authors.lastname: Dooley
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium;
authors.forename: Pia M
authors.initials: PM
authors.lastname: Vidal
authors.affiliation: Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden; and Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Pejler
authors.affiliation: Department of Morphology, Biomedical Research Institute, Hasselt University, Diepenbeek, Belgium; sven.hendrix@uhasselt.be.
authors.forename: Sven
authors.initials: S
authors.lastname: Hendrix
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013119:Spinal Cord Injuries / Q000378:metabolism*; D053802:Tryptases / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C509190:Tpsb2 protein, mouse; D053802:Tryptases
keywords: CNS trauma; ECM remodeling; gene expression; improved outcome; mMCP6