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Mouse mast cell protease 4 suppresses scar formation after traumatic spinal cord injury
- Source :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
- Publication Year :
- 2019
- Publisher :
- NATURE PUBLISHING GROUP, 2019.
-
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. The authors thank Leen Timmermans (Hasselt University) for her help with the qPCR analysis. This study was supported by grants from Fund for Scientific Research Flanders (FWO-Vlaanderen) to S.H. (G.0389.12, G0A5813) and N.G. (1.2.917.14N), and from 'Agency for Innovation by Science and Technology in Flanders' (IWT-Vlaanderen) to T.V. (101517) and S.L. (131230).
- Subjects :
- 0301 basic medicine
lcsh:Medicine
Article
Lesion
03 medical and health sciences
Cicatrix
Mice
0302 clinical medicine
Chymases
Neurocan
Laminin
In vivo
Glial Fibrillary Acidic Protein
medicine
Animals
Mast Cells
lcsh:Science
Spinal cord injury
Spinal Cord Injuries
Multidisciplinary
biology
Chemistry
lcsh:R
Serine Endopeptidases
Chymase
Immunology in the medical area
medicine.disease
Spinal cord
Fibrosis
Cell biology
Fibronectins
Nerve Regeneration
Fibronectin
030104 developmental biology
medicine.anatomical_structure
Chondroitin Sulfate Proteoglycans
Spinal Cord
Immunologi inom det medicinska området
biology.protein
lcsh:Q
medicine.symptom
Neuroglia
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Scientific Reports, Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
- Accession number :
- edsair.doi.dedup.....728b1c1d6243086c962ab27201d03510