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J. Biol. Chem., Vol. 280, Issue 22, 21653-21660, June 3, 2005

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Wnt-7a Up-regulates Matrix Metalloproteinase-12 Expression and Promotes Cell Proliferation in Corneal Epithelial Cells during Wound Healing^*

Jungmook Lyu and Choun-Ki Joo

From the Department of Ophthalmology and Visual Science, College of Medicine, Catholic University of Korea, Seoul 137-040, Korea

Corneal wound repair involves the rapid coverage of a denuded area by residual epithelial cells. During wound healing, there are different cell behaviors in different regions of the epithelium: cell proliferation in the peripheral epithelium and cell migration in the central epithelium. We found that Wnt-7a was rapidly induced in the wounded cornea, promoted the proliferation of corneal epithelial cells, and enhanced wound closure. Matrix metalloproteinase-12 (MMP-12) was detected in the peripheral epithelium, where cell proliferation was enhanced, but was diminished in the migrating central epithelium. Wnt-7a induced the accumulation of -catenin and the activation of Rac and -catenin, and Rac synergistically induced the transcription of MMP-12. Blocking the function of MMP-12 delayed wound closure induced by Wnt-7a. Our results also suggest that, in addition to the -catenin pathway, Wnt-7a might induce a -catenin-independent pathway. By regulating the proliferation of corneal epithelial cells, Wnt-7a and MMP-12 appear to contribute to corneal wound healing.

Received for publication, January 11, 2005 , and in revised form, March 31, 2005.

^* This work was supported by Korea Health 21 R&D Project Grant 03-PJ1-PG10-20700-0002 from the Ministry of Health and Welfare of Korea. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Ophthalmology and Visual Science, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Seocho-ku, Seoul 137-040, Korea. Tel.: 822-590-2613; Fax: 822-533-3801; E-mail: ckjoo{at}catholic.ac.kr.

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