title: Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic rat models.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Nutrition and Physiology, Nihon University Graduate School of Applied Life Sciences, Kameino 1866, Fujisawa, Kanagawa 252-8516, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Kazo
authors.initials: K
authors.lastname: Kaizu
authors.forename: Kohei
authors.initials: K
authors.lastname: Uriu
authors.forename: Toshinori
authors.initials: T
authors.lastname: Noguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takagi
authors.forename: Yue Ling
authors.initials: YL
authors.lastname: Qie
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D051381:Rats; D020334:Rats, Inbred OLETF; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; D013311:Streptozocin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator