The mechanism for activation of aldosterone/mineralocorticoid receptor in life style-related diseases

我们之前报道了Rac1激活矿皮质激素受体（MR）的新机制（Nat Med 2008）。在本项目中，我们发现活性氧诱导的Rac1-MR通路的激活可引起心脏、肾脏和大脑的损伤。肾小球足细胞和肾小管细胞中的Rac1-MR激活分别导致肾小球损伤和盐敏感性高血压（JCI 2011）。我们还发现，另一种核受体糖皮质激素受体（GR）的激活，通过改变组蛋白调节，刺激肾脏交感神经活动，从而激活GR- wnk4 - ncc通路（Nat Med 2011）。这表明表观遗传调节与不同管状部位的钠重吸收的MR和GR激活密切相关。综上所述，我们确定了MR-和gr -激活两种新的盐敏感性高血压发生途径，从而为代谢综合征器官损伤的表观遗传调控提供了线索。

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.