June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
MMP14-Mediated Differential Regulation of VEGFR1, 2, & 3 Expression in Corneal Epithelial Cells vs. Corneal Keratocytes
Author Affiliations & Notes
  • Jin-Hong Chang
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Kyuyeon Han
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Dimitri Azar
    Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Jin-Hong Chang, None; Kyuyeon Han, None; Dimitri Azar, None
  • Footnotes
    Support  I01 BX002386
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 156. doi:
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      Jin-Hong Chang, Kyuyeon Han, Dimitri Azar; MMP14-Mediated Differential Regulation of VEGFR1, 2, & 3 Expression in Corneal Epithelial Cells vs. Corneal Keratocytes
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):156.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Vascular endothelial growth factor receptor 3 (VEGFR3) regulates the growth and differentiation of blood and lymphatic vessels. We hypothesized that matrix metalloproteinase 14 (MMP14)-modulated VEGFR3 expression in the corneal epithelium may influence corneal avascularity.

Methods : VEGFR3 expression was compared between wild-type and MMP14-deficient (MMP14 Δexon4) corneal epithelial cells and keratocytes. VEGFR3 protein and mRNA expression were measured by Western blot and quantitative RT-PCR analyses, respectively. Potential cleavage of VEGFR3 by catalytic MMP14 was examined in an in vitro proteolysis experiment. Mass proteomic analysis was used to identify potential nuclear proteins differentially expressed in MMP14 Δexon4 and WT corneal epithelial cells.

Results : VEGFR3 protein expression was much higher on MMP14 Δexon4 corneal epithelial cells than on wild-type cells. Additionally, 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. In contrast to epithelial cells, MMP14 Δexon4 keratocytes did not exhibit elevated VEGFR3 expression relative to wild-type keratocytes. Interestingly, in vitro proteolysis experiments showed that MMP14 does not cleave VEGFR3 in vitro as it does VEGFR1, indicating that other nuclear factors may be involved in the modulation of VEGFR3 expression by MMP14. Using LC-MS/MS proteomic analysis, we found that 39 nuclear proteins were differentially expressed between wild-type and MMP14 Δexon4 corneal epithelial cells.

Conclusions : MMP14 may regulate VEGFR3 expression at the transcriptional level on corneal epithelial cells but not on corneal keratocytes.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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