Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/28554
Title: Mouse mast cell protease 4 suppresses scar formation after traumatic spinal cord injury
Authors: VANGANSEWINKEL, Tim 
LEMMENS, Stefanie 
GEURTS, Nathalie 
Quanten, Kirsten
DOOLEY, Dearbhaile 
Pejler, Gunnar
HENDRIX, Sven 
Issue Date: 2019
Publisher: NATURE PUBLISHING GROUP
Source: SCIENTIFIC REPORTS, 9 (Art N° 3715)
Abstract: Spinal cord injury (SCI) triggers the formation of a glial and fibrotic scar, which creates a major barrier for neuroregenerative processes. Previous findings indicate that mast cells (MCs) protect the spinal cord after mechanical damage by suppressing detrimental inflammatory processes via mouse mast cell protease 4 (mMCP4), a MC-specific chymase. In addition to these immunomodulatory properties, mMCP4 also plays an important role in tissue remodeling and extracellular matrix degradation. Therefore, we have investigated the effects of mMCP4 on the scarring response after SCI. We demonstrate that the decrease in locomotor performance in mMCP4(-/-) mice is correlated with excessive scar formation at the lesion. The expression of axon-growth inhibitory chondroitin sulfate proteoglycans was dramatically increased in the perilesional area in mMCP4(-/-) mice compared to wild type mice. Moreover, the fibronectin-, laminin-, and collagen IV-positive scar was significantly enlarged in mMCP4(-/-) mice at the lesion center. A degradation assay revealed that mMCP4 directly cleaves collagen IV in vitro. On the gene expression level, neurocan and GFAP were significantly higher in the mMCP4(-/-) group at day 2 and day 28 after injury respectively. In contrast, the expression of fibronectin and collagen IV was reduced in mMCP4(-/-) mice compared to WT mice at day 7 after SCI. In conclusion, our data show that mMCP4 modulates scar development after SCI by altering the gene and protein expression patterns of key scar factors in vivo. Therefore, we suggest a new mechanism via which endogenous mMCP4 can improve recovery after SCI.
Notes: [Vangansewinkel, Tim; Lemmens, Stefanie; Geurts, Nathalie; Quanten, Kirsten; Hendrix, Sven] Hasselt Univ, Biomed Res Inst, Dept Morphol, Diepenbeek, Belgium. [Dooley, Dearbhaile] Univ Coll Dublin, Sch Med, Hlth Sci Ctr, Dublin, Ireland. [Pejler, Gunnar] Swedish Univ Agr Sci, Dept Anat Physiol & Biochem, Uppsala, Sweden. [Pejler, Gunnar] Uppsala Univ, Dept Med Biochem & Microbiol, Uppsala, Sweden.
Document URI: http://hdl.handle.net/1942/28554
ISSN: 2045-2322
e-ISSN: 2045-2322
DOI: 10.1038/s41598-019-39551-1
ISI #: 000460391500098
Rights: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Category: A1
Type: Journal Contribution
Appears in Collections:Research publications

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