Urinary plasminogen activator (uPA) is a serine protease that plays important roles in various extracellular proteolytic processes. In humans, protein C inhibitor (PCI) is known to regulate the activity of the serine proteases involved in blood coagulation, wound healing, and tumor metastasis, whereas PCI is not present in murine plasma or tissues other than the reproductive tissues. The large amount of uPA-PCI complexes found in human urine suggests that these complexes are formed in the kidneys. In the present study, we performed immunofluorescence double labeling and electron microscopic immunocytochemistry using renal tissues from humans and human PCI gene transgenic (PCI-TG) mice. In human renal tissues, PCI and uPA colocalized in the cytoplasm of renal proximal tubular epithelial cells (RPTECs), and juxtaposition of PCI and uPA immunoreactive particles was detected in the microvilli and lysosomes in the RPTECs. The intracellular distributions of PCI and uPA in the RPTECs from PCI-TG mice were similar to those observed in human RPTECs. These findings hint at the physiological roles of uPA and PCI in human kidneys, and also suggest that the PCI-TG mice will be useful for evaluating the roles of PCI in human physiological and pathological conditions.

中文翻译：

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人和人PCI基因转基因小鼠的肾小管上皮细胞中蛋白C抑制剂（PCI）和尿纤溶酶原激活剂的细胞内定位。

尿纤溶酶原激活剂（uPA）是一种丝氨酸蛋白酶，在各种细胞外蛋白水解过程中起着重要作用。在人类中，已知蛋白C抑制剂（PCI）调节参与血液凝固，伤口愈合和肿瘤转移的丝氨酸蛋白酶的活性，而在小鼠血浆或生殖组织以外的组织中则不存在PCI。在人类尿液中发现大量的uPA-PCI复合物表明这些复合物是在肾脏中形成的。在本研究中，我们使用人类和人类PCI基因转基因（PCI-TG）小鼠的肾脏组织进行了免疫荧光双标记和电子显微镜免疫细胞化学。在人的肾组织中，PCI和uPA共定位于肾近端肾小管上皮细胞（RPTEC）的细胞质中，在RPTECs的微绒毛和溶酶体中检测到了PCI和uPA免疫反应性颗粒的并置。PCI-TG小鼠的RPTEC中PCI和uPA的胞内分布与人RPTEC中观察到的相似。这些发现暗示了uPA和PCI在人的肾脏中的生理作用，也表明PCI-TG小鼠将有助于评估PCI在人的生理和病理状况中的作用。