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NBCe2 (Slc4a5) Is Expressed in the Renal Connecting Tubules and Cortical Collecting Ducts and Mediates Base Extrusion.

NBCe2 (Slc4a5) 表达于肾连接小管和皮质集合管,介导基底挤压。

  • 影响因子:3.22
  • DOI:10.3389/fphys.2020.00560
  • 作者列表:"Barbuskaite D","Pedersen FD","Christensen HL","Johnsen LØ","Praetorius J","Damkier HH
  • 发表时间:2020-05-29
Abstract

:Arterial hypertension, is a common disorder with multiple and variable etiologies. Single nucleotide polymorphism analyses have detected an association between variants in the gene encoding the electrogenic Na+:HCO3- cotransporter NBCe2 (Slc4a5), and salt-sensitive hypertension. Mice with genetic deletion of NBCe2 are hypertensive, and the cause of the blood pressure (BP) increase is believed to arise from a lack of renal NBCe2 function. The exact cellular expression of NBCe2 in the kidney tubular system is, however, not determined. Here, we find NBCe2 to be expressed predominantly in isolated connecting tubules (CNT) and cortical collecting ducts (CD) by RT-PCR. In isolated renal CNT and CCD, genetic deletion of NBCe2 leads to decreased net base extrusion. To determine the role of renal NBCe2 in the development of hypertension, we generated CNT and intercalated cell NBCe2 knockout mice by crossing an Slc4a5 lox mouse with mice expressing cre recombinase under the V-ATPase B1 subunit promotor. Although the mice displayed changes in the expression of renal membrane transporters, we did not detect hypertension in these mice by tail cuff recordings. In conclusion, while global NBCe2 deletion certainly causes hypertension this study cannot confirm the role of renal NBCe2 expression in blood pressure regulation.

摘要

: 动脉高血压是一种常见病,病因多样。单核苷酸多态性分析检测到编码电原 Na +:HCO3-共转运蛋白 NBCe2 (Slc4a5) 的基因变体与盐敏感性高血压之间存在关联。NBCe2 基因缺失的小鼠是高血压小鼠,血压 (BP) 升高的原因被认为是由于缺乏肾脏 NBCe2 功能引起的。然而,NBCe2 在肾小管系统中的确切细胞表达尚未确定。在这里,我们通过 RT-PCR 发现 NBCe2 主要在分离的连接小管 (CNT) 和皮质集合管 (CD) 中表达。在分离的肾脏 CNT 和 CCD 中,NBCe2 的遗传缺失导致净碱基挤出减少。确定肾脏 NBCe2 在高血压发展中的作用,我们通过将 Slc4a5 lox 小鼠与 V-ATPase B1 亚基启动子下表达 cre 重组酶的小鼠杂交,生成了 CNT 和嵌入细胞 NBCe2 敲除小鼠。虽然小鼠表现出肾膜转运蛋白表达的变化,但我们没有通过尾袖带记录在这些小鼠中检测到高血压。总之,虽然全球 NBCe2 缺失肯定会导致高血压,但本研究不能证实肾脏 NBCe2 表达在血压调节中的作用。

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