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E. E. Gabison, E. Huet, B. Vallée, S. Menashi; Role of CD147/EMMPRIN in Corneal Stroma Remodeling. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2938. doi: https://doi.org/.
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We previously described EMMPRIN, the metalloproteinase inducer, in the cornea and demonstrated its up-regulation in corneal ulcerations. Recently, we demonstrated that EMMPRIN was up-regulated by TGF-b and involved in promoting fibroblast-to-myofibroblast differentiation (Huet E et al Faseb J, 2008). The aim of this study is to compare the effect of EMMPRIN and TGF-b on corneal extracellular matrix remodeling.
EMMPRIN, collagen I, alpha-smooth muscle actin (alphaSMA) expression was analyzed in normal and ulcerated human corneas, as well as in stromal cells in culture using confoncal microscopy, immuno-blots, zymography and real-time PCR.
While EMMPRIN was predominantly expressed in the epithelium in normal corneas, its expression was markedly induced in stromal cells in ulcerated corneas in the anterior stroma, regularly co-localized with alphaSMA. In vitro, although recEMMPRIN or TGF-b treated corneal fibroblasts showed similar stimulation of alphaSMA, EMMPRIN and MMP-2, they had opposite effects on MMP-1 expression. Interestingly, recEMMPRIN did not modify TIMP-1 or type 1 collagen expression in corneal fibroblasts, whereas TGF-b treatment was associated with an increase in these molecules.
TGF-b and recEMMPRIN, both involved in fibroblast-to-myofibroblast differentiation, exhibit differential effects on corneal fibroblasts collagenolytic balance. EMMPRIN up-regulation in the remodeling stroma and its regulation by TGFb and cell-cell interactions suggest that it may play an important role during corneal wound healing.
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