Differential Expression of Urokinase-Type Plasminogen Activator and Its Type-1 Inhibitor During Healing of Mouse Skin Wounds

The expression of urokinase-type plasminogen activator (u-PA) and its type-1 inhibitor (PAI-1) was examined in vivo in mouse wounds by in situ hybridization and immunohistochemistry. u-PA mRNA was present in both basal and supra-basal keratinocytes in the regenerative epithelial outgrowths at the ed...

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Veröffentlicht in:Journal of investigative dermatology 1991-11, Vol.97 (5), p.803-811
Hauptverfasser: Rømer, John, Lund, Leif R., Eriksen, Jens, Ralfkiaer, Elisabeth, Zeheb, Ron, Gelehrter, Thomas D., Danø, Keld, Kristensen, Peter
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Sprache:eng
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Zusammenfassung:The expression of urokinase-type plasminogen activator (u-PA) and its type-1 inhibitor (PAI-1) was examined in vivo in mouse wounds by in situ hybridization and immunohistochemistry. u-PA mRNA was present in both basal and supra-basal keratinocytes in the regenerative epithelial outgrowths at the edge of the wounds. In the same area, PAI-1 mRNA was only present in the basal keratinocytes. u-PA protein was detected in keratinocytes in several layers of the epithelial outgrowth, whereas PAI-1 protein was confined to the basal keratinocytes and to the area of the basal membrane. The two proteins and their mRNA were not detected in normal epidermis or in normal-looking epidermis adjacent to the wounds. Fibroblast-like cells and fairly large stellate cells (possibly macrophages) in the granulation tissue underneath the wound contained both the two proteins and their mRNA. The large stellate cells, showing a strong hybridization signal for PAI-1 mRNA, were especially abundant at the border between the necrotic wound and the newly formed granulation tissue. The specificity of these results was supported by the use of two different non-overlapping antisepses probes, sense mRNA probes, antibody preparations preabsorbed with purified proteins, and Northern analysis of tissue extracts. The localized and regulated expression of u-PA and PAI-1 seen in this study may reflect that plasminogen activation plays a role in the migration of keratinocytes and connective tissue cells during reepithelialization and tissue remodeling in wound healing.
ISSN:0022-202X
1523-1747
DOI:10.1111/1523-1747.ep12486833