|Budget Amount *help
¥211,770,000 (Direct Cost : ¥162,900,000、Indirect Cost : ¥48,870,000)
Fiscal Year 2013 : ¥20,800,000 (Direct Cost : ¥16,000,000、Indirect Cost : ¥4,800,000)
Fiscal Year 2012 : ¥31,200,000 (Direct Cost : ¥24,000,000、Indirect Cost : ¥7,200,000)
Fiscal Year 2011 : ¥41,600,000 (Direct Cost : ¥32,000,000、Indirect Cost : ¥9,600,000)
Fiscal Year 2010 : ¥52,000,000 (Direct Cost : ¥40,000,000、Indirect Cost : ¥12,000,000)
Fiscal Year 2009 : ¥66,170,000 (Direct Cost : ¥50,900,000、Indirect Cost : ¥15,270,000)
We previously reported the novel mechanism of mineralocorticoid receptor (MR) activation by Rac1 (Nat Med 2008). In this project, we found that activation of Rac1-MR pathway, induced by reactive oxygen species, causes injury of the heart, kidney and brain. Rac1-MR activation in glomerular podocytes and renal tubular cells causes glomerular damage and salt-sensitive hypertension (JCI 2011), respectively.
We also found that activation of glucocorticoid receptor (GR), another nuclear receptor, stimulates renal sympathetic activity resulting in activation of GR-WNK4-NCC pathway by changing histone modulation (Nat Med 2011). It suggests that epigenetic modulation is intimately involved in the MR and GR activation with sodium reabsorption in the different tubular sites.
Taken together, we identified the two novel pathways of MR- and GR-activation for the development of salt-sensitive hypertension, leading to the clue of epigenetic regulation of organ damage in metabolic syndrome.