| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Chronic kidney disease deteriorates partly because of the dysfunction of protective mechanisms. Progenitor cells of the kidney including endothelial progenitor cells (EPC) play major roles in the protective mechanisms during the development of kidney injury. Dysfunction of EPC obtained from chronic kidney disease has been pointed out and considered to contribute to the deterioration of renal function. In the present study, we clarified that aldosterone may induce EPC dysfunction via increased oxidative stress (Hypertension 2006). In addition, angiotensin II receptor blockade protects decrease in kidney stem-like cells, side population cells (Eur J Pharmacol 2007). Thus, mineralocorticoid receptor blockade, antioxidant, and angiotensin II type 1 receptor blocker are found to be able to protect and enhance progenitor function during the course of chronic kidney disease to, some extent.
Next, we investigated whether modification of epigenetics may enhance protective mechanisms of the kidney. We found that inhibition of histone deacetylase, an important determinant of epigenetic status, is involved in the regenerative response to ischemia (J Am Soc Nephrol 2008). Based on these findings, we found that inhibitor of histone deacetylase inhibits fibrotic changes of cultured renal tubular cells (J Am Soc Nephrol 2007), and ameliorates progression of chronic glomerulonephritis in mice (Stem Cells 2007). These findings clarified that histone deacetylase can be a target for treatment of chronic kidney disease.
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