Renal expression of fibrinolytic genes and tissue factor in a murine model of renal disease as a function of age.
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.
First Department of Internal Medicine, Nagoya University School of Medicine, Showa, Japan.
K
K
Yamamoto
D J
DJ
Loskutoff
H
H
Saito
D000375:Aging / Q000502:physiology*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005342:Fibrinolysis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
D017395:Plasminogen Activator Inhibitor 1; D013925:Thromboplastin; D014568:Urokinase-Type Plasminogen Activator