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Publication : Protective effects of matrix metalloproteinase-12 following corneal injury.

First Author  Chan MF Year  2013
Journal  J Cell Sci Volume  126
Issue  Pt 17 Pages  3948-60
PubMed ID  23813962 Mgi Jnum  J:245036
Mgi Id  MGI:5913815 Doi  10.1242/jcs.128033
Citation  Chan MF, et al. (2013) Protective effects of matrix metalloproteinase-12 following corneal injury. J Cell Sci 126(Pt 17):3948-60
abstractText  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 alpha-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.
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