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.

The role of homocysteine in seminal vesicles remodeling in rat

“…Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteolytic enzymes, classified into five groups: gelatinases (MMP-2 and MMP-9), mainly targeting denatured interstitial collagen (gelatin) and type I and IV collagen fibers; stromelysins (MMP-3, MMP-10, and MMP-11), targeting non-collagen molecules and proteoglycans; collagenases (MMP-1, MMP-8, MMP-13, and MMP-18), targeting fibrillar forms of collagen; matrilysins (MMP-7 and MMP-26) and MT-MMPs (MMP-14, MMP-15, MMP-16, MMP-17, MMP-24, and MMP-25), a group of transmembrane enzymes not only cleaving ECM components, but also activating other MMPs [9][10][11][12]. MMPs are implicated in remodeling of many connective tissues in physiological and pathological processes such as reproduction, embryonic development, morphogenesis, angiogenesis and fibrosis of such organs as liver, kidney and pulmonary [13][14][15][16][17][18].…”

Limited versus total epithelial debridement ocular surface injury: Live fluorescence imaging of hemangiogenesis and lymphangiogenesis in Prox1-GFP/Flk1::Myr-mCherry mice

“…A number of causal pro- and anti-angiogenic factors have been identified, including members of the VEGF family of ligands and receptors, bFGFs, and matrix metalloproteinases (MMPs) [3, 20], while anti-angiogenic factors include other members of the VEGF family in addition to angiostatin and endostatin [29]. The corneal epithelium produces both pro- and anti-angiogenic factors.…”

Biological modulation of corneal epithelial wound healing

“…During the process of epithelial renewal and repair, the secretion of ECM components is altered, influencing the expression of matrix metalloproteinases (MMPs) (29)(30)(31) . MMPs belong to the extracellular endoproteinase family and, under physiological conditions, are responsible for catalyzing ECM molecules, such as collagen, proteoglycans, and fibronectin, helping to maintain the structure and functions of the cornea (32) .…”

“…The expression and performance of MMPs are regulated by GFs and cytokines, such as interleukin-1 (IL-1) and transforming growth factor beta (TGF-β), enabling cell migration and tissue repair success (33,34) . One example of this process is the elevated expression of MMP-2 and MMP-9 following an epithelial injury, resulting in the migration of keratocytes (32,34,35) .…”