Protective effects of matrix metalloproteinase-12 following corneal injury
Open Access
- 1 January 2013
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 126 (17), 3948-3960
- https://doi.org/10.1242/jcs.128033
Abstract
Corneal scarring due to injury is a leading cause of blindness worldwide and results from dysregulated inflammation and angiogenesis during wound healing. Here we demonstrate that the extracellular matrix metalloproteinase MMP12 (macrophage metalloelastase) is an important regulator of these repair processes. Chemical injury resulted in higher expression of the fibrotic markers α-smooth muscle actin and type I collagen, and increased levels of angiogenesis in corneas of Mmp12−/− mice compared with corneas of wild-type mice. In vivo, we observed altered immune cell dynamics in Mmp12−/− corneas by confocal imaging. We determined that the altered dynamics were the result of an altered inflammatory response, with delayed neutrophil infiltration during the first day and excessive macrophage infiltration 6 days later, mediated by altered expression levels of chemokines CXCL1 and CCL2, respectively. Corneal repair returned to normal upon inhibition of these chemokines. Taken together, these data show that MMP12 has a protective effect on corneal fibrosis during wound repair through regulation of immune cell infiltration and angiogenesis.Keywords
This publication has 63 references indexed in Scilit:
- ExoS and ExoT ADP Ribosyltransferase Activities Mediate Pseudomonas aeruginosa Keratitis by Promoting Neutrophil Apoptosis and Bacterial SurvivalThe Journal of Immunology, 2012
- Experimental models to study lymphatic and blood vascular metastasisJournal of Surgical Oncology, 2011
- Matrix Metalloproteinases: Regulators of the Tumor MicroenvironmentCell, 2010
- Matrix Metalloproteinase 12-Deficiency Augments Extracellular Matrix Degrading Metalloproteinases and Attenuates IL-13–Dependent FibrosisPublished by The American Association of Immunologists ,2010
- MMP12,Lung Function, and COPD in High-Risk PopulationsNew England Journal of Medicine, 2009
- Turnover of bone marrow‐derived cells in the irradiated mouse corneaImmunology, 2008
- Noninvasive high-resolution in vivo imaging of cell biology in the anterior chamber of the mouse eyeNature Protocols, 2008
- Noninvasive in vivo imaging of pancreatic islet cell biologyNature Medicine, 2008
- Essential Role of MMP-12 in Fas-Induced Lung FibrosisAmerican Journal of Respiratory Cell and Molecular Biology, 2007
- New functions for the matrix metalloproteinases in cancer progressionNature Reviews Cancer, 2002