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E. E. Gabison, B. Vallée, C. Baudouin, I. Cochereau, E. Huet, S. Menashi; Emmprin Induction by High Osmolarity Disrupt Corneal Epithelial Barrier Through MMP Induction. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5198.
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Dry eye is a common disease that develops as a result of osmotic stress, leading to altered corneal epithelial barrier function and inflammation. MMP-9 was shown to play an important role as increased MMP-9 was observed in the tear fluid of dry eye patients and its knockout in experimental dry eye was shown to confer resistance to the epithelial disruption. We hypothesized that EMMPRIN/CD147, a known inducer of MMP production enriched in epithelial cells may be responsible, through MMP-9 upregulation, for the disruption of the epithelial layer integrity observed in this disease
We looked at the effect of high osmolarity on EMMPRIN expression, MMP-9 production and the tight junction protein occludin expression in corneal epithelial cells in culture. In order to assess the role of EMMPRIN in this regulation we used EMMPRIN siRNA in this in vitro system.
Our results show that EMMPRIN expression was increased by increasing sodium chloride concentrations, reaching maximum at 70 mM NaCl, and was associated with a parallel increase in MMP-9. This was associated with a loss of occludin at the cell-cell junctions. The effect of EMMPRIN was confirmed by silencing its expression with siRNA which inhibited MMP-9 increase and prevented the loss of occludin from the cell surface.
These results were reinforced by our data from patients with dry eye, showing that tear substitution reduced EMMPRIN and MMP-9 expression. All together, our results suggeste a role for EMMPRIN in the disruption of the epithelial barrier through MMP induction
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