Rømer J, Lund L R, Eriksen J, Ralfkiaer E, Zeheb R, Gelehrter T D, Danø K, Kristensen P
Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark.
J Invest Dermatol. 1991 Nov;97(5):803-11. doi: 10.1111/1523-1747.ep12486833.
The expression of urokinase-type plasminogen activator (u-PA) and its type-1 inhibitor (PAI-1) was examined in vivo in mouse wounds by in situ hybridization and immunohistochemistry. u-PA mRNA was present in both basal and suprabasal keratinocytes in the regenerative epithelial outgrowths at the edge of the wounds. In the same area, PAI-1 mRNA was only present in the basal keratinocytes. u-PA protein was detected in keratinocytes in several layers of the epithelial outgrowth, whereas PAI-1 protein was confined to the basal keratinocytes and to the area of the basal membrane. The two proteins and their mRNA were not detected in normal epidermis or in normal-looking epidermis adjacent to the wounds. Fibroblast-like cells and fairly large stellate cells (possibly macrophages) in the granulation tissue underneath the wound contained both the two proteins and their mRNA. The large stellate cells, showing a strong hybridization signal for PAI-1 mRNA, were especially abundant at the border between the necrotic wound and the newly formed granulation tissue. The specificity of these results was supported by the use of two different non-overlapping antisense probes, sense mRNA probes, antibody preparations preabsorbed with purified proteins, and Northern analysis of tissue extracts. The localized and regulated expression of u-PA and PAI-1 seen in this study may reflect that plasminogen activation plays a role in the migration of keratinocytes and connective tissue cells during reepithelialization and tissue remodeling in wound healing.
通过原位杂交和免疫组织化学技术，在小鼠伤口的体内环境中检测了尿激酶型纤溶酶原激活剂（u-PA）及其1型抑制剂（PAI-1）的表达。u-PA mRNA存在于伤口边缘再生上皮生长区的基底和基底上层角质形成细胞中。在同一区域，PAI-1 mRNA仅存在于基底角质形成细胞中。在上皮生长的多层角质形成细胞中检测到了u-PA蛋白，而PAI-1蛋白局限于基底角质形成细胞和基底膜区域。在正常表皮或伤口附近外观正常的表皮中未检测到这两种蛋白质及其mRNA。伤口下方肉芽组织中的成纤维细胞样细胞和相当大的星状细胞（可能是巨噬细胞）同时含有这两种蛋白质及其mRNA。PAI-1 mRNA显示出强烈杂交信号的大星状细胞，在坏死伤口与新形成的肉芽组织之间的边界处尤为丰富。使用两种不同的非重叠反义探针、正义mRNA探针、用纯化蛋白预吸附的抗体制剂以及组织提取物的Northern分析，支持了这些结果的特异性。本研究中观察到的u-PA和PAI-1的局部化和调节性表达可能反映出纤溶酶原激活在伤口愈合的再上皮化和组织重塑过程中，对角质形成细胞和结缔组织细胞的迁移发挥了作用。
