MMP12 Inhibits Corneal Neovascularization and Inflammation through Regulation of CCL2

• Published in: Scientific reports 2019-08, Vol.9 (1), p.11579-13, Article 11579
• Main Authors: Wolf, Marie, Clay, Selene M., Zheng, Siyu, Pan, Peipei, Chan, Matilda F.
• Format: Article
• Language: English
• Subjects: 13; 13/51; 14/63; 38/77; 45/90; 631/80/2373; 631/80/304; 631/80/84; 64/110; 692/699/3161/3163; 82/1; 96; Animals; CC chemokine receptors; CCR2 protein; Chemokine CCL2 - metabolism; Cornea; Cornea - blood supply; Cornea - metabolism; Cornea - pathology; Corneal Neovascularization - etiology; Corneal Neovascularization - metabolism; Corneal Neovascularization - pathology; Disease Models, Animal; Female; Fibrosis; Homeostasis; Humanities and Social Sciences; Inflammation; Inflammation - etiology; Inflammation - metabolism; Inflammation - pathology; Macrophages; Male; Matrix metalloproteinase; Matrix Metalloproteinase 12 - metabolism; Metalloproteinase; Mice; Monocyte chemoattractant protein 1; multidisciplinary; Protective Factors; Protein interaction; Science; Science (multidisciplinary); Vascularization; Wounding
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-47831-z

Following corneal injury, coordinated cellular and protein interactions occur at the wound site to restore tissue homeostasis. Regulation of this response is required to prevent the development of chronic inflammation, abnormal neovascularization, and fibrosis. The chemokine CCL2 and its primary receptor CCR2 are key regulators of the inflammatory and neovascular responses to injury. In this study, we investigated the role of macrophage-associated matrix metalloproteinase 12 (MMP12) in the regulation of CCL2 and CCR2 after corneal wounding. Using two corneal injury models, we examined the temporal and spatial expression of CCL2 and CCR2 in Mmp12 −/− and wild-type (WT) mice. Our data showed that MMP12 downregulated CCL2 and CCR2 expression in a manner dependent on the timing and mechanism of injury. We also examined the effect of CCL2 on the injury response in Mmp12 −/− and WT corneas. We found that macrophage infiltration and neovascularization following CCL2 blockade was significantly reduced in Mmp12 −/− corneas as compared with WT corneas. These findings indicate that MMP12 inhibits corneal inflammation and neovascularization after injury through its regulation of CCL2.