| Budget Amount *help |
¥3,810,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
In this study, we investigated whether adiponectin would inhibit the progression of diabetic nephropathy in vitro and in vivo. The mesangial cell proliferation appears to play an early and pivotal role in the pathogenesis of progressive glomerular injury. Therefore, we first demonstrated the adiponectin inhibited resistin-induced DNA synthesis as measured by [3H]-thymidine incorporation on rat cultured mesangial cells. Consistent with the thymidine incorporation data, adiponectin diminished the resistin induced phosphorylation of MAPK.
Next, we investigated the effect of adiponectin on diabetic nephropathy in experimental diabetic rats by overexpression the adipinectin protein using intravenous administration of an adenovirus (Ad-Adipo). Male Wistar rats,. 6-week-old, were used. Diabetic rat was induced by intraperitoneal injection of streptozotocin (STZ) (80 mg/kg) in citrate buffer (pH 4.5). At 10 weeks after the STZ injection, Ad-lacZ or Ad-Adipo was injected intravenous. The effects of adiponectin on urinary protein excretion were observed after 3 weeks post Ad injection. Body weight, plasma fasting glucose levels, plasma fasting insulin levels, total cholesterol levels, HDL-cholesterol levels, and plasma creatinine levels are no difference between two groups, whereas and urinary protein/creatinine exertion ratio levels were significantly determined by 25%.
In kidney, TGF-a mRNA expression was significantly decreased in the Ad-Adipo rats compared with Ad-lacZ rats, whereas collagen type I and IV mRNA expression were no difference between two groups. In addition, nehrin mRNA expression in kidney was significantly increased in the Ad-Adipo rats. Interestingly, iNOS, ET-1, and PAI-1 mRNA expression were significantly increased, whereas eNOS mRNA expression was in kidney with the ad-Adipo rats compared with Ad-lacZ rats.
These results suggest a role of adiponectin in the prevention of diabetic nephropathy and show that adiponectin is a potential therapeutic strategy.
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