| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
We have reported that proteinuria induced the expression of brain specific protein, glia maturation factor-β (GMF) in the kidney (latiney Int 2002). It caused vulnerability to oxidative injury, resulting in apoptosis in cultured renal proximal tubular cells (T. Biol. Chem., 2003). To analyze the pathophysiological roles of GMF expression, we constructed transgenic mice expressing GMF (GMF-TG) and induced ischemia-reperfusion (IR) injury.
The real-time PCR revealed that the expression of GMF in the kidney of GMF-TG was increased approximately eight times higher than that in wild type mice (C57BL/6) kidney. We performed Tunel assay to evaluate apoptotic cells in the kidney. It demonstrated that Tunel positive cells were significantly increased in the kidney of GMF-TG, indicating that GMF expression induced apoptosis in vivo, too. Thus, we hypothesized that I/R injury might cause severer damages in GMF-TG mice kidney than in wild type mice kidney. After right nephrectomy, ischemic injury w
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as induced by clamping of left renal artery and vein for 16 min. Surprisingly, serum creatinine levels were significantly low in GMF-TG compared to in normal mice (GMF-TG:0.611±0.07 mg/d1 versus normal:0.841±0.19 mg/d1, p<0.05, n=5 and 6, respectively) at 24hrs after reperfusion. Real-time PCR demonstrated that the expression of several mRNA such as p21, PAI-1 and CTGF in the normal and GMF-TG kidney before induction of I/R injury showed no significant differences. P21, PAI-1 and CTGF expression was up-regulated 24hr after I/R injury in wild type mice kidney (p21:60.3±12.4, PAI-1:90.6±18.2, CTGF:4.9±1.6 fold increases; n=4). It, however, was significantly decreased in GMF-TG kidney (p21:23.3±4.1, PAI-1:39.2±8.4, CTGF:2.4±0.3 fold increases; n=4) compared to those in normal mice at 24hr after 1/R. Data are provided as fold increase of each gene expression in wild type and GMF-TG mice kidney without I/R injury.
Conclusion: The data indicated that GMF expression in vivo might have protective roles on I/R injury, although its expression resulted in apoptosis because of vulnerability to oxidative injury in vitro. Less
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