| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
Renal fibrosis, a main determinant for the prognosis of progressive renal disease, is usually preceded by interstitial inflammation. Therefore, it is hypothesized that prevention of inflammation is an important clue to retard the disease progression. Nuclear factor kappaB (NF-κB) is a ubiquitous transcription factor that plays a crucial role in inflammation. It has been recognized that continuous activation of NF-κB leads to the development of renal fibrosis. Several studies using Rho-kinase (ROCK) inhibitor, Y27632 or fasudil suggested the role of ROCK in tissue inflammation and fibrosis. In order to examine the interaction between NF-κB and ROCK, we examine the effects of fasudil on renal inflammation and fibrotic changes using rat model of chronic tacrolimus nephropathy and another renal fibrosis model induced by unilateral ureteral obstruction (UUO). Fasudil did not affect NF-κB activation, renal inflammation or fibrosis in tacrolimus nephropathy whereas it partially attenuated these changes in UUO rats. These results may indicate that relative role of ROCK differs with different etiology of renal fibrosis. It was also suggested that ROCK is involved, at least in part, in the activation of NF-κB observed in UUO rats. We also observed in UUO rats that a phenolic compound, curcumin partially attenuated NF-κB activation, renal inflammation or fibrosis but such effects were smaller than those observed using specific NF-κB inhibitor, pyrrolidine dithiocarbamate. It is important to search anti-inflammatory strategies via different route to prevent the progression of chronic renal disease.
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