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E.E. Gabison, E. Steinfels–Kohn, S. Mourah, A. Mauviel, T. Hoang–Xuan, S. Menashi; Role of EMMPRIN in Matrix Metalloproteinases Induction During Corneal Wound Healing . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4882.
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Purpose: To investigate whether EMMPRIN, a membrane glycoprotein known to induce MMP production by stromal fibroblasts in contact with tumor cells, was involved in matrix metalloproteinase induction during corneal wound healing. Methods:We studied MMPs and EMMPRIN expression in normal and wounded human corneas, as well as in corneal epithelial and stromal cells in culture in response to cytokines, using confoncal microscopy, zymography, western blot analysis and real time PCR. We investigated whether direct epithelio–stromal interaction in vitro was responsible for MMP induction in corneal fibroblasts. Results: While EMMPRIN was predominantly expressed in the normal corneal epithelium, this molecule was induced in ulcerated corneas in the anterior stroma. This upregulation of EMMPRIN at the ulcerated site was associated with an increase in MMP–2 and MMP–9 secretion and activation, as shown by real time PCR and zymography analysis of corneal tissue sections. In culture, EMMPRIN was differentially regulated by cytokines, induced by TGF–ß in both epithelial and stromal cells and by EGF only in epithelial cells. Co–culture of corneal epithelial and stromal cells was responsible for an MMP–2 induction in the fibroblasts at the epithelial boundary. Similarly, purified corneal epithelial cell membranes induced MMP–1 and MMP–2 in corneal fibroblasts, both at the mRNA and protein level. Conclusions:EMMPRIN at the epithelial cell surface may induce MMP production in corneal fibroblasts at the subepithelial layer during corneal wound healing.
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