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Haijing Sun, Ilham Bettahi, Fushin X Yu; Impaired Injury-induced expression of Serpine1 and delayed epithelial wound healing in diabetic mouse corneas. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4702.
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Patients with diabetes mellitus (DM) are at an increased risk for developing corneal complications including delayed wound healing. The objectives of this study were to characterize the expression and the role of Sperine1 in delayed epithelial wound healing in diabetic mouse corneas.
C57BL/6 mice were induced to develop diabetes by intraperitoneal injection of streptozotocin (STZ). The differential expression of the members of the UPA proteolytic system detected by cDNA array was verified by realtime PCR, Western blotting, and/or immunohistochemistry. The role of Serpine1 was determined by supplementing DM corneas with recombinant protein or by neutralizing antibody blocking of Serpine1 in normal and diabetic cornea. The effects of Serpine1 alteration on MMP-3 and Plau expression and MMP-3 activities were assessed by realtime PCR and MMP-3 enzyme assay.
Among 5 members of the UPA proteolytic system, the expressions of Plau, Plaur, and Serpine1 were upregulated in response to wounding while the up-regulation of Plaur and Serpine1 was dampened by hyperglycemia. In healing epithelia, Plau and Serpine1 were abundantly expressed at the leading edge of healing epithelia of normal and to a less extent of diabetic corneas. Inhibition of Serpine1 significantly delayed epithelial wound closure in normal but not diabetic corneas, whereas exogenously supplemented Serpine1 accelerated epithelial wound healing in diabetic corneas. The expression of Plau and MMP3 at the mRNA levels and MMP3 enzymatic activities were correlated to the Serpine1 levels and/or the rate of epithelial wound closure. The wound-induced and hyperglycemia-suppressed expression pattern of Serpine1 was confirmed in ex vivo human diabetic corneas.
Serpine1 plays a role in mediating epithelial wound healing and its impaired expression DM corneas may contribute to the delayed wound healing. Hence, Serpine1 may be used to treat delayed epithelial wound healing in diabetic patients.
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