INCREASED EXPRESSION OF SLC2A9 DECREASES URATE EXCRETION FROM THE KIDNEY
INCREASED EXPRESSION OF SLC2A9 DECREASES URATE EXCRETION FROM THE KIDNEY
复制标题
DOI：
10.1080/15257770.2011.628354
复制
发表时间：
2011-01-01
影响因子：
1.3
通讯作者：
Sakurai, Hiroyuki
中科院分区：
文献类型：
--
作者：
Kimura, Toru;Amonpatumrat, Sirirat;Sakurai, Hiroyuki
尿酸盐是人体内嘌呤的最终代谢物。肾尿酸盐的处理在临床上很重要，因为重吸收不足或排泄不足分别会导致低尿酸血症或高尿酸血症。我们发现尿酸-阴离子交换器URAT1定位于肾小管的顶端，电压驱动的尿酸外流转运体URATv1表达于肾近端小管的基底外侧。URAT1和URATv1对肾尿酸盐的重吸收至关重要，因为实验数据表明，这些转运蛋白的功能丧失导致了低尿酸血症。虽然通过这些转运蛋白在尿酸盐处理上提供增强功能的突变尚不清楚，但我们已经为URAT1或URATv1构建了肾脏特异性转基因(TG)小鼠来研究这个问题。在我们的研究中，每个转基因都在小鼠URAT1启动子的控制下，因此转基因表达被定向到肾脏。URAT1和URATv1转基因小鼠的血尿酸浓度与野生型(WT)小鼠无显著差异。URAT1转基因小鼠的尿酸盐排泄量与WT小鼠相似，而URATv1转基因小鼠的尿酸盐排泄量高于WT小鼠。我们的结果表明，肾脏中URATv1功能亢进可导致尿酸重吸收增加，并可能导致高尿酸血症的发生。
Urate is the final metabolite of purine in humans. Renal urate handling is clinically important because under-reabsorption or underexcretion causes hypouricemia or hyperuricemia, respectively. We have identified a urate-anion exchanger, URAT1, localized at the apical side and a voltage-driven urate efflux transporter, URATv1, expressed at the basolateral side of the renal proximal tubules. URAT1 and URATv1 are vital to renal urate reabsorption because the experimental data have illustrated that functional loss of these transporter proteins affords hypouricemia. While mutations affording enhanced function via these transporter proteins on urate handling is unknown, we have constructed kidney-specific transgenic (Tg) mice for URAT1 or URATv1 to investigate this problem. In our study, each transgene was under the control of the mouse URAT1 promoter so that transgene expression was directed to the kidney. Plasma urate concentrations in URAT1 and URATv1 Tg mice were not significantly different from that in wild-type (WT) mice. Urate excretion in URAT1 Tg mice was similar to that in WT mice, while URATv1 Tg mice excreted more urate compared with WT. Our results suggest that hyperfunctioning URATv1 in the kidney can lead to increased urate reabsorption and may contribute to the development of hyperuricemia.