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Expression of type-1 plasminogen activator inhibitor in the kidney of diabetic rat models
Hiromi Hagiwara1, Kazo Kaizu, Kohei Uriu
1Department of Nutrition and Physiology, Nihon University Graduate School of Applied Life Sciences, Kameino 1866, Fujisawa, Kanagawa 252-8516, Japan.
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.
Insights
Diabetic nephropathy involves intrarenal coagulation and fibrinolysis. This study found increased plasminogen activator inhibitor-1 (PAI-1) gene expression in diabetic rat kidneys, suggesting its role in disease development.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic nephropathy pathogenesis involves intrarenal coagulation and fibrinolysis.
- Gene expression of fibrinolytic factors in diabetic nephropathy remains unclear.
- This study investigates fibrinolytic factor gene expression in diabetic rat kidneys.
Purpose of the Study:
- To determine the gene expression of fibrinolytic factors in the kidneys of diabetic rats.
- To clarify the role of fibrinolysis in diabetic nephropathy.
- To investigate the impact of diabetes on PAI-1, tPA, and uPA gene expression.
Main Methods:
- Utilized streptozotocin (STZ)-induced type 1 diabetes and Otsuka Long-Evans Tokushima Fatty (OLETF) type 2 diabetes rat models.
- Examined renal gene expression of plasminogen activator inhibitor-1 (PAI-1), tissue-type PA (tPA), and urokinase-type PA (uPA) via real-time PCR.
- Investigated PAI-1 mRNA localization using in situ hybridization.
Main Results:
- Renal PAI-1 mRNA levels were elevated in both STZ-induced (60-80% increase) and OLETF (2.5-fold increase) diabetic rats.
- Insulin treatment normalized increased PAI-1 expression in STZ-induced diabetic rats.
- tPA and uPA mRNA levels were decreased in OLETF rats compared to controls.
- PAI-1 mRNA was localized to intraglomerular and tubular epithelial cells.
Conclusions:
- Renal PAI-1 gene expression is significantly upregulated in both type 1 and type 2 diabetic rat models.
- Altered gene expression of fibrinolytic factors, particularly PAI-1, likely contributes to the development and pathogenesis of diabetic nephropathy.
