Renal Unit, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Mol Aspects Med. 2013 Apr-Jun;34(2-3):313-22. doi: 10.1016/j.mam.2012.12.003.
Urea transporters (UTs) belonging to the solute carrier 14 (SLC14) family comprise two genes with a total of eight isoforms in mammals, UT-A1 to -A6 encoded by SLC14A2 and UT-B1 to -B2 encoded by SLC14A1. Recent efforts have been directed toward understanding the molecular and cellular mechanisms involved in the regulation of UTs using transgenic mouse models and heterologous expression systems, leading to important new insights. Urea uptake by UT-A1 and UT-A3 in the kidney inner medullary collecting duct and by UT-B1 in the descending vasa recta for the countercurrent exchange system are chiefly responsible for medullary urea accumulation in the urinary concentration process. Vasopressin, an antidiuretic hormone, regulates UT-A isoforms via the phosphorylation and trafficking of the glycosylated transporters to the plasma membrane that occurs to maintain equilibrium with the exocytosis and ubiquitin-proteasome degradation pathways. UT-B isoforms are also important in several cellular functions, including urea nitrogen salvaging in the colon, nitric oxide pathway modulation in the hippocampus, and the normal cardiac conduction system. In addition, genomic linkage studies have revealed potential additional roles for SLC14A1 and SLC14A2 in hypertension and bladder carcinogenesis. The precise role of UT-A2 and presence of the urea recycling pathway in normal kidney are issues to be further explored. This review provides an update of these advances and their implications for our current understanding of the SLC14 UTs.
尿素转运蛋白（UTs）属于溶质载体 14（SLC14）家族，哺乳动物中共有两个基因，总共编码 8 种同工型，即 SLC14A2 编码的 UT-A1 至 -A6 和 SLC14A1 编码的 UT-B1 至 -B2。最近，人们通过转基因小鼠模型和异源表达系统，致力于研究参与 UTs 调节的分子和细胞机制，从而获得了重要的新见解。肾脏内髓集合管中的 UT-A1 和 UT-A3 以及逆流交换系统中的降支直血管中的 UT-B1 负责摄取尿素，主要负责在尿浓缩过程中在内髓积聚尿素。加压素是一种抗利尿激素，通过磷酸化和糖基化转运蛋白向质膜的运输来调节 UT-A 同工型的运输，这种运输发生是为了与外排和泛素-蛋白酶体降解途径保持平衡。UT-B 同工型在包括结肠中尿素氮的回收、海马中的一氧化氮途径调节和正常心脏传导系统等多种细胞功能中也很重要。此外，基因组连锁研究表明 SLC14A1 和 SLC14A2 在高血压和膀胱癌发生中可能具有潜在的额外作用。UT-A2 的精确作用和正常肾脏中尿素再循环途径的存在是需要进一步探讨的问题。本文综述了这些进展及其对我们目前对 SLC14 UTs 的理解的影响。
