About this item:

42 Views | 132 Downloads

Author Notes:

Baoxue Yang, baoxuee@bjmu.edu.cn

X. G., S. Z., J. H., and Y. L. data curation; X. G. and J. H. software; X. G. formal analysis; X. G., S. Z., A. M., M. L., and G. C. investigation; X. G., A. M., Y. L., H. Z., G. C., and B. Y. methodology; X. G. writing-original draft; A. M. and B. Y. funding acquisition; H. Z. validation; G. C. and B. Y. supervision; B. Y. conceptualization; B. Y. resources; B. Y. writing-review and editing.

The authors declare that they have no conflicts of interest with the contents of this article.

Subject:

Research Funding:

This work was supported by National Natural Science Foundation of China Grants 81620108029, 81974083, 81330074, and 81800388 (to A. M. and B. Y.); Beijing Natural Science Foundation Grant 7172113 (to B. Y.); and China Postdoctoral Science Foundation Grant 2018M630049 (to A. M.).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • animal model
  • CRISPR
  • Cas9
  • gene knockout
  • kidney
  • renal physiology
  • UT-A1
  • urea transporter
  • diuresis
  • electrolyte metabolism
  • UT-A
  • MICE LACKING
  • MEMBRANE ACCUMULATION
  • WATER CHANNEL
  • MESSENGER-RNA
  • CLONING
  • LOCALIZATION
  • KNOCKOUT
  • GENE
  • PHOSPHORYLATION

The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

Tools:

Journal Title:

JOURNAL OF BIOLOGICAL CHEMISTRY

Volume:

Volume 295, Number 29

Publisher:

, Pages 9893-9900

Type of Work:

Article | Final Publisher PDF

Abstract:

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 UTA1–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 UTA1 represents a promising diuretic target.

Copyright information:

© 2020 Geng et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
Export to EndNote