Differential expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in early and late gestational mouse skin and skin wounds.
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.
Huang
Eunice Y
EY
Department of Surgery, Keck School of Medicine, University of Southern California, Childrens Hospital of Los Angeles, Los Angeles, California, USA.
Wu
Huayang
H
Island
Eddie R
ER
Chong
Sheree S
SS
Warburton
David
D
Anderson
Kathryn D
KD
Tuan
Tai-Lan
TL
D000818:Animals; D002921:Cicatrix / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000473:pathology* / Q000503:physiopathology; D005865:Gestational Age; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis*; D010960:Plasminogen Activators / Q000032:analysis*; D011247:Pregnancy; D049188:Prenatal Injuries; D015842:Serine Proteinase Inhibitors / Q000032:analysis*; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*; D014945:Wound Healing / Q000502:physiology; D014950:Wounds, Penetrating / Q000150:complications / Q000473:pathology* / Q000503:physiopathology
D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator