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

Kyu-Yeon      Han; Daoud      C. Fahd; Makambo      Tshionyi; Norma      Allemann; Sandeep      Jain; Jin-Hong      Chang; Dimitri      T. Azar

doi:10.2174/092986612803521639

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.

Keywords: Basic FGF, corneal angiogenesis, ERK, MT1-MMP, Ras, VEGF-A, homeostasis, pro-angiogenic effect, Basic fibroblast growth factor (bFGF), vascular endothelial growth factor.