Yamamoto K, Loskutoff D J, Saito H
First Department of Internal Medicine, Nagoya University School of Medicine, Showa, Japan.
Semin Thromb Hemost. 1998;24(3):261-8. doi: 10.1055/s-2007-995852.
Abnormal expression of fibrinolytic genes [e.g., tissue-type and urokinase-type plasminogen activators (t-PA and u-PA) and their specific inhibitor (PAI-1)] and of the procoagulant molecule tissue factor (TF), has been reported in various types of renal diseases. In this review, the expression pattern of these genes was demonstrated in two murine models of renal disease. One is acute renal failure due to microthrombosis under septic conditions, using endotoxin-treated mice, and the other one is lupus nephritis observed in female MRL lpr/lpr mice. Quantitative reverse transcription-polymerase chain reaction analysis and in situ hybridization were employed to investigate the expression of their mRNAs in tissues from endotoxin-treated mice or from MRL lpr/lpr mice. A dramatic increase in PAI-1 activity in plasma and in PAI-1 mRNA in the kidneys was observed in both models, and this increase appeared to correlate with fibrin deposition in the renal microvasculature and with the progression of lupus nephritis. In addition to these changes in PAI-1, decreases in u-PA mRNA and increases in TF mRNA were demonstrated in the kidneys from lupus-prone mice as a function of age. Similar changes were also observed in the kidneys from endotoxin-treated mice. The induction of PAI-1 and TF, and the decrease in u-PA expression in the kidneys of lupus-prone or of endotoxemic mice may promote the formation of renal microthrombi and thus contribute to the progression of renal damage in these models.
在各种类型的肾脏疾病中，均有关于纤溶基因[如组织型和尿激酶型纤溶酶原激活剂（t-PA和u-PA）及其特异性抑制剂（PAI-1）]以及促凝分子组织因子（TF）异常表达的报道。在本综述中，这些基因的表达模式在两种肾脏疾病小鼠模型中得到了证实。一种是使用内毒素处理的小鼠，在脓毒症条件下因微血栓形成导致的急性肾衰竭；另一种是在雌性MRL lpr/lpr小鼠中观察到的狼疮性肾炎。采用定量逆转录-聚合酶链反应分析和原位杂交技术，研究内毒素处理小鼠或MRL lpr/lpr小鼠组织中这些基因mRNA的表达情况。在两种模型中均观察到血浆中PAI-1活性和肾脏中PAI-1 mRNA显著增加，且这种增加似乎与肾微血管中的纤维蛋白沉积以及狼疮性肾炎的进展相关。除了PAI-1的这些变化外，随着年龄增长，狼疮易感小鼠肾脏中u-PA mRNA减少，TF mRNA增加。在内毒素处理小鼠的肾脏中也观察到了类似变化。狼疮易感或内毒素血症小鼠肾脏中PAI-1和TF的诱导以及u-PA表达的降低，可能促进肾微血栓的形成，从而导致这些模型中肾损伤的进展。
