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E.E. Gabison, E. Huet, S. Mourah, S. Menashi, T. Hoang–Xuan; EMMPRIN and MMP Regulation by Cytokine and Direct Epithelio–Stromal Interactions in the Cornea . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5029.
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We previously described EMMPRIN, the metalloproteinase inducer, in the cornea and demonstrated its upregulation during corneal healing process (E. E. Gabison et al. Am J Pathol 2005). In this study we investigated the role of cytokines and cell–cell contact in the regulation of EMMPRIN.
Material and Methods: :
MMPs and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confoncal microscopy, zymography, immunoblots and real–time PCR.
In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP–2 induction which colocalized with EMMPRIN at the epithlio–stromal boundary. In an in–vitro coculture system we demonstrated the induction and colocalization of EMMPRIN and MMP–2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN–containing purified epithelial cell membranes also induced MMP–1, MMP–2 and EMMPRIN and this was inhibited by a blocking anti–EMMPRIN antibody. Additionnaly, EMMPRIN and MMP–2 were also induced by TGF–b in corneal fibroblasts in culture.
EMMPRIN upregulation during corneal wound healing may be mediated by cell–cell interactions or by diffusible cytokines including TGF–B.
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