title: Matrix metalloproteinase 14 modulates signal transduction and angiogenesis in the cornea.
abstract: The cornea is transparent and avascular, and retention of these characteristics is critical to maintaining vision clarity. Under normal conditions, wound healing in response to corneal injury occurs without the formation of new blood vessels; however, neovascularization may be induced during corneal wound healing when the balance between proangiogenic and antiangiogenic mediators is disrupted to favor angiogenesis. Matrix metalloproteinases (MMPs), which are key factors in extracellular matrix remodeling and angiogenesis, contribute to the maintenance of this balance, and in pathologic instances, can contribute to its disruption. Here, we elaborate on the facilitative role of MMPs, specifically MMP-14, in corneal neovascularization. MMP-14 is a transmembrane MMP that is critically involved in extracellular matrix proteolysis, exosome transport, and cellular migration and invasion, processes that are critical for angiogenesis. To aid in developing efficacious therapies that promote healing without neovascularization, it is important to understand and further investigate the complex pathways related to MMP-14 signaling, which can also involve vascular endothelial growth factor, basic fibroblast growth factor, Wnt/β-catenin, transforming growth factor, platelet-derived growth factor, hepatocyte growth factor or chemokines, epidermal growth factor, prostaglandin E2, thrombin, integrins, Notch, Toll-like receptors, PI3k/Akt, Src, RhoA/RhoA kinase, and extracellular signal-related kinase. The involvement and potential contribution of these signaling molecules or proteins in neovascularization are the focus of the present review.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Christy M
authors.initials: CM
authors.lastname: Cunningham
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Kyu-Yeon
authors.initials: KY
authors.lastname: Han
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chang
authors.affiliation: Institute of Medical Science, University of Tokyo, Tokyo, Japan.
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.affiliation: Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Zhongjun
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, Illinois, USA. Electronic address: dazar@uic.edu.
authors.forename: Dimitri T
authors.initials: DT
authors.lastname: Azar
mesh_terms: D000818:Animals; D003315:Cornea / Q000201:enzymology* / Q000473:pathology; D016510:Corneal Neovascularization / Q000175:diagnosis / Q000201:enzymology*; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D015398:Signal Transduction
chemical_list: C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14
keywords: MMP-14; VEGF-A; bFGF; corneal neovascularization; signal transduction