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C.–K. Joo, J. Lyu; Wnt 7a Promotes Matrix Metalloprotainase 12–Dependent Proliferation in Human Corneal Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2110.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: During wound healing, proliferation and migration are two different cell behaviors in two different regions of the epithelium. The cell migration and proliferative responses are believed to be regulated by several cues. However, the extracellular cues that induce the compartmentalized responses to these events during wound healing are poorly understood. Methods: Corneoscleral rims taken from human donor were used to culture the primary human corneal epithelial (HCE) cells. Each scleral rim removed endothelial layer was treated with Dispase II for 15 min, and epithelial cells were then isolated. For the assays used in this study, the cells were plated on a diluted Matrigel matrix, which is similar to the basement membrane of corneal epithelium, and incubated in a growth factor– and serum–free for 24 hrs. Results: Here, we found that Wnt 7a is rapidly induced in a wounded cornea, and Wnt 7a promotes the proliferation of corneal epithelial cells and enhances the wound closure. In addition, matrix metalloproteinase (MMP)–12 expression was detected in the peripheral epithelium, where the cells enhanced the rate of proliferation, but diminished in the migrating central epithelium. The transcriptional activity of MMP–12 was found to be responsive to Wnt 7a. In particular, Wnt 7a induced the accumulation of ß–catenin and the activation of Rac, and ß–catenin and Rac synergistically induced the transcription of this gene. The effect of MMP–12 on cell proliferation was also examined in order to evaluate functional consequences of MMP–12 induction. The function–blocking of MMP–12 delayed the Wnt 7a–induced wound closure. Conclusions: These results indicate that in addition to the ß–catenin pathway, Wnt 7a might induce the ß–catenin–independent pathway, and Wnt 7a and MMP–12 can regulate the proliferation of the corneal epithelial cells, which can contribute to the coverage of a defective area during corneal wound healing.
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