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Corneal Epithelial MT1-MMP Inhibits Vascular Endothelial Cell Proliferation and Migration

Azar, Dimitri T MD; Casanova, Fabio H MD; Mimura, Tatsuya MD, PhD; Jain, Sandeep MD; Zhou, Zhongjun PhD; Han, Kyu Yeon PhD; Chang, Jin-Hong PhD

doi: 10.1097/ICO.0b013e3181b1165d
Basic Investigation

Purpose: To determine the effects of corneal epithelial membrane-type 1 matrix metalloproteinase (MT1-MMP) on vascular endothelial migration and proliferation.

Methods: We generated immortalized wild-type, MT1-MMP knockout and MT1-MMP knock-in corneal epithelial cells. Calf pulmonary arterial endothelial (CPAE) cell proliferation and Boyden chamber migration were assayed.

Results: Conditioned media from MT1-MMP epithelial knockout cells significantly increased CPAE proliferation 5-bromo-2'-deoxy-uridine (BrdU) incorporation, and CPAE migration as compared with wild-type epithelial cells. Conditioned media from knock-in cells reversed the increase in CPAE proliferation, BrdU incorporation and CPAE migration. Knock-in cells transfected with mutant MT1-MMP (E240A) did not abrogate the reversal effect.

Conclusions: Corneal epithelial MT1-MMP is antiangiogenic. This antiangiogenic activity does not require the catalytic domain.

From the *Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL; †Schepens Eye Research Institute, Harvard Medical School, Boston, MA; ‡Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, MA; and §Department of Biochemistry, The University of Hong Kong, Hong Kong.

Received for publication March 2, 2009; revision received April 14, 2009; accepted May 3, 2009.

Supported by National Institutes of Health grants EY10101 (D.T.A.), EY001792 (D.T.A.), and EY14048 (J.H.C.) and an unrestricted departmental grant from Research to Prevent Blindness.

Reprints: Dimitri T. Azar, MD, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 West Taylor Street, Chicago, IL 60612 (e-mail: dazar@uic.edu).

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