Jensen P J, Lavker R M
Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia 19104-6142, USA.
Cell Growth Differ. 1996 Dec;7(12):1793-804.
Many lines of evidence support an involvement of urokinase plasminogen activator (uPA) and its type 1 inhibitor (PAI-1) in the migration of a variety of cells, including normal keratinocytes and carcinoma lines. In the present study, uPA expression was found to be a characteristic not just of migratory but also of proliferative keratinocytes. A variety of naturally occurring and experimentally induced epidermal hyperproliferative conditions were examined in mice, including fetal and neonatal epidermis, tape-stripped epidermis, and epidermis from which the hairs had been gently plucked. In all cases, epidermal hyperproliferation was accompanied by elevated levels of uPA mRNA (as measured by in situ hybridization) and activity (as measured by zymography). uPA mRNA was predominantly localized in the basal and immediately suprabasal cells, which constitute the proliferative population. To determine whether a PAI was concomitantly elevated, in situ hybridization for PAI-1 and PAI-2 was performed. PAI-2 but not PAI-1 mRNA was detected in fetal and neonatal epidermis, localized in the spinous layers. Although mRNAs for both inhibitors were induced by tape-stripping or hair-plucking, their distribution was more focal and more transient than that of uPA mRNA. These findings show that uPA, but not its usual inhibitors, is consistently elevated in the proliferative population of keratinocytes in a diverse range of hyperproliferative states. Two hypotheses are suggested by these data: (a) uPA may play a regulatory role in the activation of epidermal proliferation; or (b) uPA may be involved in the vertical migration of keratinocytes that must accompany increased cell proliferation.
许多证据支持尿激酶型纤溶酶原激活剂（uPA）及其1型抑制剂（PAI-1）参与多种细胞的迁移，包括正常角质形成细胞和癌细胞系。在本研究中，发现uPA的表达不仅是迁移性角质形成细胞的特征，也是增殖性角质形成细胞的特征。在小鼠中检查了多种自然发生的和实验诱导的表皮过度增殖情况，包括胎儿和新生儿表皮、胶带剥离的表皮以及轻轻拔毛后的表皮。在所有情况下，表皮过度增殖都伴随着uPA mRNA水平的升高（通过原位杂交测量）和活性的升高（通过酶谱分析测量）。uPA mRNA主要定位于构成增殖群体的基底细胞和紧邻基底上层的细胞中。为了确定PAI是否同时升高，进行了PAI-1和PAI-2的原位杂交。在胎儿和新生儿表皮的棘层中检测到PAI-2 mRNA，但未检测到PAI-1 mRNA。虽然两种抑制剂的mRNA都可由胶带剥离或拔毛诱导，但它们的分布比uPA mRNA更局限、更短暂。这些发现表明，在多种过度增殖状态下，uPA而非其通常的抑制剂在角质形成细胞的增殖群体中持续升高。这些数据提出了两种假设：（a）uPA可能在表皮增殖的激活中起调节作用；或（b）uPA可能参与了角质形成细胞的垂直迁移，而这种迁移必须伴随细胞增殖的增加。
