THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IS EXPRESSED BYKERATINOCYTES AT THE LEADING SKIN DURING REEPITHILIALIZATION

Expression of urokinase-type plasminogen activator receptor mRNA was e xamined in vivo in mouse skin wounds by in situ hybridization. Urokina se-type plasminogen activator receptor mRNA was found in keratinocytes at the front of the regenerative epithelial outgrowths at the edge of 12-, 48-, and 96-hour-old wounds. The signal was strongest in the ker atinocytes just beginning to move 12 h after wounding. At later timepo ints the signal was weaker, but still confined to keratinocytes at the wound edges. Using in situ hybridization, no cells expressing urokina se-type plasminogen activator receptor mRNA could be detected in norma l epidermis, in normal-looking epidermis adjacent to the wounds, in de rmis, in subcutis, or in newly formed granulation tissue. The specific ity of the results was supported by the use of antisense RNA from two different non-overlapping cDNA clones and the corresponding sense RNA probes, and by Northern analysis of tissue extracts. Together with pre vious findings on expression of urokinase-type plasminogen activator a nd its type 1 inhibitor, the localized and regulated expression of uro kinase-type plasminogen activator receptor mRNA during skin wound heal ing indicates that focal extracellular proteolysis at the cell surface generated by receptor-bound urokinase-type plasminogen activator is i mplicated in the migration of re-epithelializing keratinocytes.