Development of drug by use of protease cascade of prostasin

高血压是导致血管系统损害的重要因素之一。肾脏中的钠调节是调节血压的最重要因素之一。上皮细胞钠通道是调节钠平衡的关键蛋白。我们报道了一种新的丝氨酸蛋白酶prostasin能激活培养细胞的上皮钠通道。前列腺素在体外和体内实验中被醛固酮刺激。原发性醛固酮增多症患者尿前列腺素排泄量增加，提示前列腺素可能在血压调节中起重要作用。因此，我们利用蛋白质组学的方法研究了前列腺素在血压调节中的作用。首先，我们分离了几个激活丝氨酸蛋白酶前列腺素的蛋白质。我们已经分离出三个激活前列腺素活性的克隆。目前，我们正在对这些蛋白质进行纯化和氨基酸鉴定，该项目正在进行中。我们必须继续进行进一步的实验。

Hypertension is one of the strong factors to damage vascular system. Sodium regulation in the kidney is one of the most important factors for the regulation of blood pressure. Epithelial sodium channel is key protein in the regulation of Na balance. We reported that a new serine protease prostasin can activate epithelial sodium channel in cultured cells. Prostasin was stimulated by aldosterone in vitro and in vivo experiments. In human, urinary prostasin excretion was elevated in primary aldosteronism, suggesting that prostasin may have significant roles in the regulation of blood pressure. Therefore, we have investigated to elucidate the roles of prostasin in the regulation of blood pressure by use of proteomics. At first, we have isolated several proteins which activate serine protease prostasin. We have already isolated three clones which activated prostasin activity. We now under experiments to purify and identify of amino acid of these proteinsThis projects is now underway. We must continue further experiments.