PUBLICATION
Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration
- Authors
- Xu, S., Webb, S.E., Lau, T.C.K., Cheng, S.H.
- ID
- ZDB-PUB-180510-3
- Date
- 2018
- Source
- Scientific Reports 8: 7199 (Journal)
- Registered Authors
- Cheng, Shuk Han, Webb, Sarah E.
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Cell Proliferation
- Chemokine CCL2/chemistry
- Chemokine CCL2/genetics
- Chemokine CCL2/metabolism*
- Chemokine CCL2/pharmacology
- Chemotaxis/drug effects
- Cryosurgery
- Dipeptides/pharmacology
- Gene Expression Regulation
- Heart/drug effects
- Heart Injuries/genetics
- Heart Injuries/metabolism*
- Heart Injuries/rehabilitation
- Interleukin-8/chemistry
- Interleukin-8/genetics
- Interleukin-8/metabolism*
- Interleukin-8/pharmacology
- Leukocytes/cytology
- Leukocytes/drug effects
- Leukocytes/metabolism
- Macrophages/cytology
- Macrophages/drug effects
- Macrophages/metabolism
- Matrix Metalloproteinase 13/genetics
- Matrix Metalloproteinase 13/metabolism*
- Matrix Metalloproteinase 9/genetics
- Matrix Metalloproteinase 9/metabolism*
- Matrix Metalloproteinase Inhibitors/pharmacology
- Myocytes, Cardiac/cytology
- Myocytes, Cardiac/drug effects
- Myocytes, Cardiac/metabolism
- Proteolysis
- Regeneration/physiology*
- Signal Transduction
- Zebrafish
- PubMed
- 29740050 Full text @ Sci. Rep.
Citation
Xu, S., Webb, S.E., Lau, T.C.K., Cheng, S.H. (2018) Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration. Scientific Reports. 8:7199.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping