Urokinase plasminogen activator (uPA) is a positive regulator of outer root sheath keratinocyte proliferation

Urokinase plasminogen activator (uPA), a serine proteinase, is important in the development and epidermal wound healing, and seems to play a regulatory role in the proliferation of mouse epidermal keratinocytes (KC). In the present study, we found detectable uPA expression in outer root sheath (ORS) KC in the early anagen phase in mouse vibrissa follicles, but not in the late anagen or in the telogen and categen phases. uPA was also detected in ORS KC cultured from neonatal mice vibrissa. Specific exogenous inhibitors of uPA, amiloride and uPA antibody, significantly reduced the proliferation of ORS KC. Thus uPA is consistently elevated in the hyperproliferative hair follicle KC, and inhibition of the enzyme decreases hair follicle KC proliferation. We deduce that uPA is a very important mediator of the hair follicle cycle because its activity correlates with ORS KC proliferation.