Differential expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in early and late gestational mouse skin and skin wounds.

Abstract

Early gestation fetal mouse skin heals without scars. Plasminogen activator inhibitor-1 (PAI-1) has been associated with postnatal organ fibrosis. We hypothesized that the relative balance between urokinase-type plasminogen activator (uPA) and PAI-1 expression in favor of uPA prevents scarring in early fetal skin wounds, whereas a change in favor of PAI-1 in late gestation results in wound scarring. To evaluate uPA and PAI-1 expression, 1-mm skin wounds were made in E14.5 and E18 mice and harvested 24, 48, or 96 hours postwounding. Aprotinin (2 mg/ml)-coated beads were injected into selected E14.5 wounds. Normal skin and skin wounds were evaluated for uPA, PAI-1, and collagen expression. We showed that in normal skin uPA level is higher in E14.5 than in E18 mice, while PAI-1 is lower in E14.5 than in E18 mice. After wounding, E14.5 wounds show a moderate increase in uPA and a minimal increase in PAI-1. E18 wounds show a transient increase in uPA but a significant, sustained increase in PAI-1. Addition of aprotinin to E14.5 wounds causes an increase in collagen deposition. We conclude that the differential expression of uPA and PAI-1 in the skin of early vs. late gestation mice may contribute to the degree of scar formation seen after cutaneous injury.