Title:MMP14 Regulates VEGFR3 Expression on Corneal Epithelial Cells
Volume: 23
Issue: 12
Author(s): Kyu-Yeon Han, Jin-Hong Chang and Dimitri T. Azar
Affiliation:
Keywords:
MMP14, VEGFR3, corneal epithelial cell, angiogenesis, corneal keratocyte, lymphangiogenesis.
Abstract: Vascular endothelial growth factor receptor 3 (VEGFR3) regulates the growth and differentiation
of blood and lymphatic vessels. To determine whether matrix metalloproteinase 14
(MMP14) modulates VEGFR3 expression in the corneal epithelium to influence the avascularity of
the cornea, VEGFR3 expression was compared between wild-type and MMP14-deficient (MMP14
Δexon4) corneal epithelial cells. Western blot analysis showed that VEGFR3 protein expression was
higher on MMP14 Δexon4 corneal epithelial cells than on wild-type cells, and quantitative RT-PCR
analysis showed that VEGFR3 gene expression was highly induced in MMP14 Δexon4 corneal
epithelial cells but not in wild-type corneal epithelial cells or wild-type and MMP14 Δexon4 corneal
keratocytes. Unlike in epithelial cells, MMP14 Δexon4 keratocytes did not express relatively higher
levels of VEGFR3 than wild-type keratocytes. Interestingly, in vitro proteolysis experiments showed
that MMP14 does not cleave VEGFR3 in vitro as it does VEGFR1, indicating that other genes may
be involved in the modulation of VEGFR3 expression by MMP14. Using proteomic analysis to identify
candidate factors, we found that 39 nuclear proteins were differentially expressed between wildtype
and MMP14 Δexon4 corneal epithelial cells. These findings suggest that MMP14 may regulate
VEGFR3 expression at the transcriptional level on corneal epithelial cells but not on corneal keratocytes.
