Abstract:
In humans, uric acid is an end-product of purine metabolism. Urate excretion from the human kidney is tightly regulated by reabsorption and secretion. At least eleven genes have been identified as human renal urate transporters. However, it remains unclear whether all renal tubular cells express the same set of urate transporters. Here, we show renal tubular cells are divided into three distinct cell populations for urate handling. Analysis of healthy human kidneys at single-cell resolution revealed that not all tubular cells expressed the same set of urate transporters. Only 32% of tubular cells were related to both reabsorption and secretion, while the remaining tubular cells were related to either reabsorption or secretion at 5% and 63%, respectively. These results provide physiological insight into the molecular function of the transporters and renal urate handling on single-cell units. Our findings suggest that three different cell populations cooperate to regulate urate excretion from the human kidney, and our proposed framework is a step forward in broadening the view from the molecular to the cellular level of transport capacity.
摘要:
在人类中,尿酸是嘌呤代谢的最终产物。从人类肾脏排泄的尿酸盐通过重吸收和分泌而受到严格调节。至少11个基因已被鉴定为人肾尿酸盐转运蛋白。然而,目前尚不清楚是否所有肾小管细胞都表达同一组尿酸盐转运蛋白.这里,我们显示肾小管细胞分为三种不同的细胞群进行尿酸盐处理。以单细胞分辨率对健康人肾脏的分析表明,并非所有肾小管细胞都表达同一组尿酸盐转运蛋白。只有32%的肾小管细胞与重吸收和分泌有关,而其余的肾小管细胞与重吸收或分泌有关,分别为5%和63%,分别。这些结果提供了对转运蛋白和肾尿酸盐在单细胞单元上的处理的分子功能的生理学见解。我们的研究结果表明,三种不同的细胞群协同调节人肾脏尿酸盐的排泄,我们提出的框架是在从分子水平到细胞水平的转运能力方面向前迈出的一步。