Journal of cellular physiology
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Several proteases and their specific inhibitors modulate the interdependent processes of cell migration and matrix proteolysis as part of the global program of trauma repair. Expression of plasminogen activator inhibitor type-1 (PAI-1), a serine protease inhibitor (SERPIN) important in the control of barrier proteolysis and cell-to-matrix adhesion, for example, is spatially-temporally regulated following epithelial denudation injury in vitro as well as in vivo. PAI-1 mRNA/protein synthesis was induced early after epidermal monolayer scraping and restricted to keratinocytes comprising the motile cohort closely recapitulating, thereby, similar events during cutaneous healing. ⋯ PAI-1-/- keratinocytes, in fact, had a significant wound healing defect evident even within the first 6 h following monolayer denudation injury. Addition of active PAI-1 protein to PAI-/- keratinocytes rescued the migratory phenotype that that approximating wild-type cells. These findings validate use of the present keratinocyte model to investigate injury-related controls on PAI-1 gene regulation and, collectively, implicate participation of PAI-1 in two distinct phases of epidermal wound repair.