MT1-MMP Modulates bFGF-Induced VEGF-A Expression in Corneal Fibroblasts

Abstract

The cornea is physiologically avascular. Following a corneal injury, wound healing often proceeds without neovascularization (NV); however, corneal NV may be induced during wound healing in certain inflammatory, infectious, degenerative, and traumatic states. Such states disrupt the physiologic balance between pro-angiogenic and antiangiogenic mediators, favoring angiogenesis. Contributors to such states are matrix metalloproteinases (MMPs), which are key factors in both extracellular matrix remodeling and angiogenesis. Similarly, vascular endothelial growth factor A (VEGF-A) and basic fibroblast growth factor (bFGF) exert pro-angiogenic effects. Here, we elaborate on the facilitative role of MMPs-specifically Membrane Type 1 MMP (MT1-MMP, MMP14)-in corneal NV. Additionally, we provide new insight into the signaling relating to MT1-MMP, Ras, and ERK in the bFGF-induced VEGF-A expression pathways within the corneal fibroblasts.