Tamura Yuma, Mori Nobuyoshi, Xu Bin, Nakamura Takahiro, Yamakoshi Seiko, Hirose Takuo, Ito Osamu, Totsune Kazuhito, Takahashi Kazuhiro, Kohzuki Masahiro
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine.
Tohoku J Exp Med. 2016 Jul;239(3):185-92. doi: 10.1620/tjem.239.185.
Water deprivation activates the renin-angiotensin system. We have hypothesized that the renal expression of (pro)renin receptor ((P)RR), a specific receptor for renin and prorenin, could be changed under dehydration. Moreover, plasma levels of soluble (P)RR (s(P)RR) comprising of the extracellular domain of (P)RR may reflect the renal (P)RR expression. In the present study, we therefore aimed to clarify changes of plasma s(P)RR concentrations and kidney tissue (P)RR levels using rats with dehydration. Male Wister-Kyoto rats were divided into two groups; dehydrated (DH) rats deprived of water for 72 hours with free access to food, and control rats. Plasma s(P)RR concentrations measured by enzyme-linked immunosorbent assay were significantly lower in DH rats (6.94 ± 2.08 ng/mL, mean ± SD, n = 5) than in control (12.54 ± 2.00 ng/mL, n = 5) (p < 0.05). Western blot analysis confirmed lower expression levels of s(P)RR in plasma in DH rats than in control. By contrast, western blot analysis showed higher levels of full-length (P)RR and lower levels of furin (an enzyme responsible for generation of s(P)RR from full-length (P)RR) in the kidney tissues obtained from DH rats compared to control. There was no significant difference in the renal (P)RR mRNA levels between DH rats and control. These findings suggest that water deprivation may elevate the renal full-length (P)RR levels via reducing the expression of furin. Increased full-length (P)RR may contribute to the up-regulation of the renal renin-angiotensin system and the production of concentrated urine under dehydration.
缺水会激活肾素-血管紧张素系统。我们推测，（前）肾素受体（(P)RR）作为肾素和前肾素的特异性受体，其在肾脏中的表达可能会在脱水状态下发生改变。此外，由(P)RR细胞外结构域组成的可溶性(P)RR（s(P)RR）的血浆水平可能反映肾脏(P)RR的表达情况。因此，在本研究中，我们旨在通过脱水大鼠来阐明血浆s(P)RR浓度和肾脏组织(P)RR水平的变化。雄性Wister-Kyoto大鼠被分为两组；脱水（DH）组大鼠禁食72小时但可自由进食，另一组为对照组大鼠。通过酶联免疫吸附测定法测得的DH组大鼠（6.94±2.08 ng/mL，平均值±标准差，n = 5）血浆s(P)RR浓度显著低于对照组（12.54±2.00 ng/mL，n = 5）（p < 0.05）。蛋白质印迹分析证实，DH组大鼠血浆中s(P)RR的表达水平低于对照组。相比之下，蛋白质印迹分析显示，与对照组相比，从DH组大鼠获得的肾脏组织中全长(P)RR水平较高，而弗林蛋白酶（一种负责从全长(P)RR生成s(P)RR的酶）水平较低。DH组大鼠和对照组之间肾脏(P)RR mRNA水平无显著差异。这些发现表明，缺水可能通过降低弗林蛋白酶的表达来提高肾脏全长(P)RR水平。全长(P)RR增加可能有助于在脱水状态下上调肾脏肾素-血管紧张素系统并产生浓缩尿液。
