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.
Jensen
P J
PJ
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142, USA.
Lavker
R M
RM
D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement; D018859:Hair Follicle / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010960:Plasminogen Activators / Q000494:pharmacology; D012867:Skin / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*