title: Matrix metalloproteinase 9 modulates collagen matrices and wound repair.
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.
authors.affiliation: Cellular and Molecular Pathology Graduate Program, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Danny C
authors.initials: DC
authors.lastname: LeBert
authors.affiliation: Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Jayne M
authors.initials: JM
authors.lastname: Squirrell
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Rindy
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Broadbridge
authors.affiliation: Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Lui
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Zakrzewska
authors.affiliation: Laboratory for Optical and Computational Instrumentation, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.affiliation: Institute of Biology, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands.
authors.forename: Annemarie H
authors.initials: AH
authors.lastname: Meijer
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA Department of Pediatrics, University of Wisconsin-Madison, Madison, WI 53706, USA huttenlocher@wisc.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Huttenlocher
mesh_terms: D058500:Animal Fins / Q000166:cytology / Q000276:immunology; D000818:Animals; D003094:Collagen / Q000502:physiology*; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D060172:Morpholinos; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D060172:Morpholinos; D053491:Proteinase Inhibitory Proteins, Secretory; D029961:Zebrafish Proteins; C543576:clint1a protein, zebrafish; C527985:spint1a protein, zebrafish; D003094:Collagen; D020780:Matrix Metalloproteinase 9
keywords: Inflammation; Mmp9; Repair; SHG imaging; Zebrafish