Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Clin Sci (Lond). 2019 Jan 8;133(1):75-82. doi: 10.1042/CS20180194. Print 2019 Jan 15.
Distal nephron of the kidney plays key roles in fluid volume and electrolyte homeostasis by tightly regulating reabsorption and excretion of Na, K, and Cl Studies to date demonstrate the detailed electrolyte transport mechanisms in principal cells of the cortical collecting duct, and their regulation by renin-angiotensin-aldosterone system (RAAS). In recent years, however, accumulating data indicate that intercalated cells, another cell type that is present in the cortical collecting duct, also play active roles in the regulation of blood pressure. Notably, pendrin in β-intercalated cells not only controls acid/base homeostasis, but is also one of the key components controlling salt and K transport in distal nephron. We have recently shown that pendrin is regulated by the co-ordinated action of angiotensin II (AngII) and aldosterone, and at the downstream of AngII, mammalian target of rapamycin (mTOR) signaling regulates pendrin through inhibiting the kinase unc51-like-kinase 1 and promoting dephosphorylation of mineralocorticoid receptor (MR). In this review, we summarize recent advances in the current knowledge on the salt transport mechanisms in the cortical collecting duct, and their regulation by the RAAS.
肾脏的远曲小管通过严格调节钠、钾和氯的重吸收和排泄，在体液量和电解质稳态中发挥关键作用。迄今为止的研究表明，皮质集合管主细胞中的电解质转运机制及其受肾素-血管紧张素-醛固酮系统（RAAS）的调节。然而，近年来越来越多的数据表明，另一种存在于皮质集合管中的细胞类型——闰细胞，在血压调节中也发挥着积极的作用。值得注意的是，β闰细胞中的 Pendrin 不仅控制酸碱稳态，还是调节远曲小管盐和钾转运的关键成分之一。我们最近表明，Pendrin 通过血管紧张素 II（AngII）和醛固酮的协同作用来调节，在 AngII 的下游，雷帕霉素靶蛋白（mTOR）信号通过抑制激酶 unc51 样激酶 1 和促进盐皮质激素受体（MR）的去磷酸化来调节 Pendrin。在这篇综述中，我们总结了目前关于皮质集合管中盐转运机制及其受 RAAS 调节的最新知识进展。
