Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic rat models

• Published in: Thrombosis research 2003, Vol.111 (4), p.301-309
• Main Authors: Hagiwara, Hiromi, Kaizu, Kazo, Uriu, Kohei, Noguchi, Toshinori, Takagi, Ichiro, Qie, Yue Ling, Seki, Taiichiro, Ariga, Toyohiko
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - analysis; Body Weight; Cardiology. Vascular system; Diabetes; Diabetes Mellitus, Experimental - blood; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - chemically induced; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Kidney - metabolism; Kidney - pathology; Male; Medical sciences; Organ Size; Plasminogen Activator Inhibitor 1 - metabolism; Rats; Rats, Inbred OLETF; Rats, Sprague-Dawley; Renal gene expression; Streptozocin; Tissue Plasminogen Activator - metabolism; Tissue-type plasminogen activator; Type-1 plasminogen activator inhibitor; Urokinase-type plasminogen activator; Urokinase-Type Plasminogen Activator - metabolism
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2003.09.023

Introduction: Intrarenal coagulation and fibrinolysis are thought to be involved in the pathogenesis of diabetic nephropathy. However, gene expression of fibrinolytic factors in diabetic nephropathy has not been clearly defined. Therefore we determined the gene expression of fibrinolytic factors in the kidneys of diabetic rats. Materials and methods: As a model of type1 diabetes male Sprague–Dawley rats were used. They were divided into three groups: control, streptozotocin (STZ)-induced diabetic, and insulin-treated diabetic. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were used as a model of type 2 diabetes; and Long-Evans Tokushima Otsuka (LETO) rats, as the control. Renal gene expressions of type-1 plasminogen activator inhibitor (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) were examined by real-time PCR. Localization of PAI-1 mRNA was investigated by in situ hybridization. Results: Renal PAI-1 mRNA levels (versus control) were increased by 60–80% in STZ-induced diabetic rats (10 days or 3 weeks post STZ injection); and insulin treatment reduced this increased expression to the control level. In OLETF rats (38 weeks old), the renal PAI-1 mRNA level was 2.5-fold higher than that in age-matched LETO rats. Both tPA and uPA mRNA levels were significantly lower than those in LETO rats. PAI-1 mRNA was observed in intraglomerular cells and tubular epithelial cells of both models. Conclusions: Renal PAI-1 gene expression is up-regulated in both type 1 and type 2 diabetic rats, and changes in gene expressions of fibrinolytic factors may play important roles in the development and pathogenesis of diabetic nephropathy.