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

被引:34
作者
Hagiwara, H
Kaizu, K
Uriu, K
Noguchi, T
Takagi, I
Qie, YL
Seki, T
Ariga, T
机构
[1] Nihon Univ, Grad Sch Appl Life Sci, Dept Nutr & Physiol, Fujisawa, Kanagawa 2528516, Japan
[2] Univ Occupat & Environm Hlth, Sch Med, Kidney Ctr, Kitakyushu, Fukuoka 8078555, Japan
[3] Univ Occupat & Environm Hlth, Sch Med, Dept Internal Med 1, Kitakyushu, Fukuoka 8078555, Japan
关键词
type-1 plasminogen activator inhibitor; tissue-type plasminogen activator; urokinase-type plasminogen activator; renal gene expression; diabetes;
D O I
10.1016/j.thromres.2003.09.023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:301 / 309
页数:9
相关论文
共 42 条
[1]  
ADLER S, 1994, J AM SOC NEPHROL, V5, P1165
[2]   STRUCTURE AND FUNCTION OF THE KIDNEY IN DIABETIC GLOMERULOSCLEROSIS CORRELATIONS BETWEEN MORPHOLOGICAL AND FUNCTIONAL PARAMETERS [J].
BADER, R ;
BADER, H ;
GRUND, KE ;
MACKENSENHAEN, S ;
CHRIST, H ;
BOHLE, A .
PATHOLOGY RESEARCH AND PRACTICE, 1980, 167 (2-4) :204-216
[3]   ECM DEGRADATION BY CULTURED HUMAN MESANGIAL CELLS IS MEDIATED BY A PA/PLASMIN/MMP-2 CASCADE [J].
BARICOS, WH ;
CORTEZ, SL ;
ELDAHR, SS ;
SCHNAPER, HW .
KIDNEY INTERNATIONAL, 1995, 47 (04) :1039-1047
[4]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[5]   Direct binding of Smad3 and Smad4 to critical TGFβ-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene [J].
Dennler, S ;
Itoh, S ;
Vivien, D ;
ten Dijke, P ;
Huet, S ;
Gauthier, JM .
EMBO JOURNAL, 1998, 17 (11) :3091-3100
[6]   Cholesterol feeding accentuates the cyclosporine-induced elevation of renal plasminogen activator inhibitor type 1 [J].
Duymelinck, C ;
Dauwe, SEH ;
Nouwen, EJ ;
DeBroe, ME ;
Verpooten, GA .
KIDNEY INTERNATIONAL, 1997, 51 (06) :1818-1830
[7]   Interstitial fibrosis in hypercholesterolemic rats: Role of oxidation, matrix synthesis, and proteolytic cascades [J].
Eddy, AA ;
Liu, E ;
McCulloch, L .
KIDNEY INTERNATIONAL, 1998, 53 (05) :1182-1189
[8]   Plasminogen activator inhibitor-1 and the kidney [J].
Eddy, AA .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2002, 283 (02) :F209-F220
[9]   High glucose reduces generation of plasmin activity by mesangial cells [J].
Fisher, EJ ;
McLennan, SV ;
Yue, DK ;
Turtle, JR .
MICROVASCULAR RESEARCH, 1997, 53 (02) :173-178
[10]   Evaluation of glomerular lesion and abnormal urinary findings in OLETF rats resulting from a long-term diabetic state [J].
Fukuzawa, Y ;
Watanabe, Y ;
Inaguma, D ;
Hotta, N .
JOURNAL OF LABORATORY AND CLINICAL MEDICINE, 1996, 128 (06) :568-578