The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism
The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism
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尿素转运蛋白 UT-A1 在尿素依赖性尿液浓缩机制中起主导作用
DOI：
10.1074/jbc.ra120.013628
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发表时间：
2020-07-17
影响因子：
4.8
通讯作者：
Yang, Baoxue
中科院分区：
文献类型：
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作者：
Geng, Xiaoqiang;Zhang, Shun;Yang, Baoxue
尿素转运蛋白是一个在多种组织中表达的尿素选择性通道蛋白家族，在哺乳动物肾脏的尿浓缩机制中发挥重要作用。以往的研究表明，敲除尿素转运蛋白（UT）-B、UT-A1/A3或所有UT导致尿素选择性利尿，表明尿素转运蛋白在尿浓缩中具有重要作用。在这里，我们试图确定UT-A1在尿浓缩机制中的作用，在一个新开发的UT-A1基因敲除小鼠模型。从表型上看，UT-A1基因敲除小鼠的日尿量几乎是WT小鼠的3倍，是全UT基因敲除小鼠的82%，并且UT-A1基因敲除小鼠的尿渗透压显著低于WT小鼠。在24小时限水、急性尿素负荷或高蛋白（40%）摄入后，UT-A1基因敲除小鼠无法增加尿浓缩能力。与所有UT敲除小鼠相比，UT-A1敲除小鼠表现出相似的每日尿量升高和尿渗透压降低，表明尿素选择性尿浓度受损。我们的实验结果表明，UT-A1在尿素依赖性尿浓缩机制中具有主导作用，这表明UT-A1是一个有前途的利尿靶点。
Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1–knockout mouse model. Phenotypically, daily urine output in UT-A1–knockout mice was nearly 3-fold that of WT mice and 82% of all-UT–knockout mice, and the UT-A1–knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1–knockout mice were unable to increase urine-concentrating ability. Compared with all-UT–knockout mice, the UT-A1–knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.