The knockout of urea transporter-B improves the hemorheological properties of erythrocyte

Geng, Xiaoqiang; Lei, Tianluo; Zhou, Hong; Yao, Weijuan; Xin, Weihong; Yang, Baoxue

doi:10.3233/ch-16174

Cited by 5 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…UT-A2 is localized in the lower half of the thin descending limb of Henle's loops in short-looped nephrons and in the initial inner medulla (IM) segments of the thin descending limb in long-looped nephrons (7,(15)(16)(17). UT-B, the only member derived from gene Slc14a1, is expressed in renal descending vasa recta and multiple extrarenal tissues (18)(19)(20)(21)(22)(23)(24).…”

mentioning

confidence: 99%

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

Geng

Zhang

et al. 2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

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

Geng

Zhang

et al. 2020

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…These inhibitors have been proven useful for not only the drug discovery programs but also uncovering other roles of urea transport in new disease areas. For example, cell volume dysregulation by Hs UT-B–facilitated urea transport was assessed with a selective inhibitor UTB inh -14 in neuroinflammation and in erythrocyte deformation ( 4 , 16 , 17 ), further adding to the profile of urea channel inhibitors as potential therapeutics for neurodegenerative diseases ( 4 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

Structural characterization of human urea transporters UT-A and UT-B and their inhibition

Chi,

Dietz,

Tang

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

In this study, we present the structures of human urea transporters UT-A and UT-B to characterize them at molecular level and to detail the mechanism of UT-B inhibition by its selective inhibitor, UTB inh -14. High-resolution structures of both transporters establish the structural basis for the inhibitor’s selectivity to UT-B, and the identification of multiple binding sites for the inhibitor will aid with the development of drug lead molecules targeting both transporters. Our study also discovers phospholipids associating with the urea transporters by combining structural observations, native MS, and lipidomics analysis. These insights improve our understanding of urea transporter function at a molecular level and provide a blueprint for a structure-guided design of therapeutics targeting these transporters.

show abstract

Urea Transporters in Health and Disease

Klein

Sands

2020

Studies of Epithelial Transporters and Ion Channels

View full text Add to dashboard Cite

The knockout of urea transporter-B improves the hemorheological properties of erythrocyte

Abstract: The data indicate that UT-B is involved in the regulation of hemorheology, which suggests that UT-B may be a potential therapeutic target for improving the hemorheology in some metabolic and hereditary diseases.

Cited by 5 publications

References 26 publications

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

Structural characterization of human urea transporters UT-A and UT-B and their inhibition

Urea Transporters in Health and Disease

Contact Info

Product

Resources

About