Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism
Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism
复制标题
细降肢尿素转运在肾脏尿素处理和尿液浓缩机制中的作用
DOI：
10.1152/ajprenal.00404.2011
复制
发表时间：
2011-12-01
影响因子：
4.2
通讯作者：
Yang, Baoxue
中科院分区：
文献类型：
--
作者：
Lei, Tianluo;Zhou, Lei;Yang, Baoxue
Lei T，Zhou L，莱顿AT，Zhou H，Zhao X，Bankir L，Yang B.细降支尿素转运在肾脏尿素处理和尿液浓缩机制中的作用。美国肾脏生理学杂志301：F1251-F1259，2011年。首次发表于2011年8月17日; doi：10.1152/ajprenal.00404.2011。尿素转运蛋白UT-A2和UT-B分别在亨利氏袢的细降支和降直血管的上皮细胞中表达。为了研究它们在尿液浓缩机制中的作用和可能的相互作用，通过在具有UT-B基因敲除的胚胎干细胞中靶向缺失UT-A2启动子来产生UT-A2和UT-B双敲除（UT-A2/B敲除）小鼠模型。UT-A2/B基因敲除小鼠缺乏可检测的UT-A2和UT-B转录物和蛋白，并显示正常的存活和生长。UT-A2/B基因敲除小鼠的日尿量显著高于野生型小鼠，但低于UT-B基因敲除小鼠。UT-A2/B基因敲除小鼠的尿渗透压介于UT-B基因敲除小鼠和野生型小鼠之间。急性尿素负荷或蛋白质摄入慢性变化后，尿渗透压和流速、血浆和尿尿素浓度以及非尿素溶质浓度的变化表明UT-A2在尿素在髓质内的进行性蓄积中起作用。这些结果表明，在野生型小鼠中，UT-A2通过尿素从Henle氏短袢的细降支流出促进尿素吸收。此外，UT-B基因敲除小鼠中的UT-A2缺失通过减少从下行肢体到外周循环的尿素损失部分地补救了由UT-B缺失引起的尿浓缩缺陷;相反，尿素通过亨利氏环和集合管返回到内部髓质。
Lei T, Zhou L, Layton AT, Zhou H, Zhao X, Bankir L, Yang B. Role of thin descending limb urea transport in renal urea handling and the urine concentrating mechanism. Am J Physiol Renal Physiol 301: F1251-F1259, 2011. First published August 17, 2011; doi:10.1152/ajprenal.00404.2011.-Urea transporters UT-A2 and UT-B are expressed in epithelia of thin descending limb of Henle's loop and in descending vasa recta, respectively. To study their role and possible interaction in the context of the urine concentration mechanism, a UT-A2 and UT-B double knockout (UT-A2/B knockout) mouse model was generated by targeted deletion of the UT-A2 promoter in embryonic stem cells with UT-B gene knockout. The UT-A2/B knockout mice lacked detectable UT-A2 and UT-B transcripts and proteins and showed normal survival and growth. Daily urine output was significantly higher in UT-A2/B knockout mice than that in wild-type mice and lower than that in UT-B knockout mice. Urine osmolality in UT-A2/B knockout mice was intermediate between that in UT-B knockout and wild-type mice. The changes in urine osmolality and flow rate, plasma and urine urea concentration, as well as non-urea solute concentration after an acute urea load or chronic changes in protein intake suggested that UT-A2 plays a role in the progressive accumulation of urea in the inner medulla. These results suggest that in wild-type mice UT-A2 facilitates urea absorption by urea efflux from the thin descending limb of short loops of Henle. Moreover, UT-A2 deletion in UT-B knockout mice partially remedies the urine concentrating defect caused by UT-B deletion, by reducing urea loss from the descending limbs to the peripheral circulation; instead, urea is returned to the inner medulla through the loops of Henle and the collecting ducts.