Jensen P J, Lavker R M
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142, USA.
J Invest Dermatol. 1999 Feb;112(2):240-4. doi: 10.1046/j.1523-1747.1999.00494.x.
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.
表皮是一种自我更新的组织，必须维持基础增殖速率并对各种干扰刺激作出反应。角质形成细胞增殖的调节涉及多种分子，包括生长因子、离子和激素。基于将尿激酶型纤溶酶原激活剂（uPA）的表达与小鼠表皮过度增殖联系起来的相关证据，我们最近提出蛋白酶uPA也可能属于这一类别。在此我们报告，在出生后的头3天，uPA基因靶向缺失的小鼠的表皮增殖速率明显低于野生型小鼠的表皮。相比之下，新生uPA - / -小鼠毛囊基质角质形成细胞的增殖并未降低。终末分化期间角质形成细胞的垂直迁移不受影响。因此我们得出结论，uPA的缺乏与表皮增殖的降低有关。
