PUBLICATION
Matrix metalloproteinase 9 modulates collagen matrices and wound repair
- Authors
- LeBert, D.C., Squirrell, J.M., Rindy, J., Broadbridge, E., Lui, Y., Zakrzewska, A., Eliceiri, K.W., Meijer, A.H., Huttenlocher, A.
- ID
- ZDB-PUB-150528-2
- Date
- 2015
- Source
- Development (Cambridge, England) 142(12): 2136-46 (Journal)
- Registered Authors
- Huttenlocher, Anna, Meijer, Annemarie H., Zakrzewska, Ania
- Keywords
- none
- Datasets
- GEO:GSE28110
- MeSH Terms
-
- Animal Fins/cytology
- Animal Fins/immunology
- Animals
- Collagen/physiology*
- Inflammation/genetics
- Inflammation/immunology
- Matrix Metalloproteinase 9/genetics
- Matrix Metalloproteinase 9/physiology*
- Morpholinos
- Neutrophil Infiltration/genetics
- Neutrophil Infiltration/immunology
- Proteinase Inhibitory Proteins, Secretory/genetics
- Wound Healing/genetics*
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- PubMed
- 26015541 Full text @ Development
Citation
LeBert, D.C., Squirrell, J.M., Rindy, J., Broadbridge, E., Lui, Y., Zakrzewska, A., Eliceiri, K.W., Meijer, A.H., Huttenlocher, A. (2015) Matrix metalloproteinase 9 modulates collagen matrices and wound repair. Development (Cambridge, England). 142(12):2136-46.
Abstract
Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping