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Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration
- Source :
- Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018), Scientific Reports
- Publication Year :
- 2018
- Publisher :
- Nature Portfolio, 2018.
-
Abstract
- In zebrafish, the role of matrix metalloproteinases (MMPs) in the inflammatory phase of heart regeneration following cryoinjury remains poorly understood. Here, we demonstrated an increase in MMP enzymatic activity and elevated expression of mmp9 and mmp13 in the injured area (IA) of hearts from as early as 1 day post-cryoinjury (dpc). Treatment with the broad-spectrum MMP inhibitor, GM6001, during the first week after cryoinjury resulted in impaired heart regeneration, as indicated by the larger scar and reduced numbers of proliferating cardiomyocytes. GM6001 also significantly reduced the number of leukocytes to the IA at 0.5 dpc to 4 dpc. Specific inhibition of both MMP-9 and MMP-13 also resulted in impaired regeneration and leukocyte recruitment. However, chemokine rescue with recombinant CXCL8 and CCL2 restored the recruitment of macrophages and the cardiac regenerative capability in GM6001-treated fish. MMP-9 and MMP-13 cleaved zebrafish CXCL8 at the same site, and the truncated form was more chemotactic than the intact form. In contrast, CCL2 did not have an MMP-9 or MMP-13 cleavage site. Together, these data suggest that MMPs might play a key role in the inflammatory phase of heart regeneration in zebrafish, by mediating leukocyte recruitment via the activation of chemokines.
- Subjects :
- 0301 basic medicine
Chemokine
Science
MMP9
Matrix metalloproteinase
CCL2
Matrix Metalloproteinase Inhibitors
Cryosurgery
GM6001
Article
03 medical and health sciences
chemistry.chemical_compound
Matrix Metalloproteinase 13
Leukocytes
Animals
Regeneration
Myocytes, Cardiac
Interleukin 8
Amino Acid Sequence
Zebrafish
Chemokine CCL2
Cell Proliferation
Multidisciplinary
biology
Chemotaxis
Macrophages
Interleukin-8
Heart
Dipeptides
biology.organism_classification
Cell biology
030104 developmental biology
chemistry
Gene Expression Regulation
Heart Injuries
Matrix Metalloproteinase 9
Proteolysis
biology.protein
Medicine
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....0c73ca9d5363ca05acd2ebcb3eadc9e6