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Corneal epithelial MT1-MMP inhibits vascular endothelial cell proliferation and migration

Dimitri T Azar1, Fabio H Casanova, Tatsuya Mimura

  • 1Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA. dazar@uic.edu

Cornea
|February 2, 2010
PubMed
Abstract

Insights

Corneal epithelial membrane-type 1 matrix metalloproteinase (MT1-MMP) inhibits blood vessel growth. This antiangiogenic effect does not depend on MT1-MMP's catalytic activity, suggesting a novel therapeutic target.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Biochemistry

Background:

  • The role of matrix metalloproteinases (MMPs) in ocular angiogenesis is complex.
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an MMP implicated in various cellular processes.
  • Understanding MT1-MMP's specific function in corneal epithelial cells is crucial for ocular health.

Purpose of the Study:

  • To investigate the impact of corneal epithelial MT1-MMP on vascular endothelial cell migration and proliferation.
  • To elucidate the mechanism by which MT1-MMP influences angiogenesis.

Main Methods:

  • Generation of immortalized wild-type, MT1-MMP knockout, and MT1-MMP knock-in corneal epithelial cell lines.
  • Assay of calf pulmonary arterial endothelial (CPAE) cell proliferation using 5-bromo-2'-deoxy-uridine (BrdU) incorporation.
  • Assessment of CPAE cell migration using Boyden chamber assays.

Main Results:

  • Conditioned media from MT1-MMP-deficient epithelial cells significantly enhanced CPAE proliferation and migration.
  • Conditioned media from MT1-MMP knock-in cells reversed these pro-angiogenic effects.
  • Transfection of knock-in cells with a catalytically inactive MT1-MMP mutant (E240A) did not alter the reversal of pro-angiogenic effects.

Conclusions:

  • Corneal epithelial MT1-MMP exhibits antiangiogenic properties.
  • The antiangiogenic activity of corneal epithelial MT1-MMP is independent of its catalytic domain.

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