Urokinase is a positive regulator of epidermal proliferation in vivo

The epidermis is a self-renewing tissue that must maintain a basal proliferative rate as well as respond to various perturbing stimuli. Regulation of keratinocyte proliferation involves diverse molecules, including growth factors, ions, and hormones. We recently proposed that a proteinase, urokinase-type plasminogen activator (uPA) may be added to this list, based on correlative evidence linking expression of uPA and murine epidermal hyperproliferation. Here we report that, during the first 3 d of life, the epidermis from mice that bear a targeted deletion of the uPA gene has a significantly lower proliferative rate than the epidermis from wild- type mice. In contrast, proliferation in the matrix keratinocytes of the hair follicles is not decreased in neonatal UPA(-/-) mice. Vertical migration of keratinocytes during terminal differentiation was not affected. We therefore conclude that lack of uPA is associated with a decrease in epidermal proliferation.