Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion.
Double knockout of carbonic anhydrase II (CAII) and Na(+)-Cl(-) cotransporter (NCC) causes salt wasting and volume depletion.
复制标题
碳酸酐酶 II (CAII) 和 Na()-Cl(-) 协同转运蛋白 (NCC) 的双重敲除会导致盐浪费和容量耗尽。
DOI：
10.1159/000356637
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Soleimani,Manoocher
中科院分区：
文献类型：
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作者：
Xu,Jie;Barone,Sharon;Brooks,Mary-Beth;Soleimani,Manoocher
噻嗪敏感性Na+-Cl-协同转运蛋白NCC和Cl-/HCO 3-交换蛋白pendrin表达于远端皮质肾单位节段的顶膜上，并介导盐的吸收，pendrin与上皮Na+通道（ENaC）和Na+依赖性氯/碳酸氢盐交换蛋白（NDCBE）协同工作，而NCC本身起作用。最近的一项研究表明，NCC和pendrin在基础条件下相互补偿损失，因此掩盖了各自在盐重吸收中的作用。碳酸酐酶II（CAII，CA 2或CAR 2）在近曲小管的酸碱转运和盐重吸收以及集合管的酸碱转运中起重要作用。具有CAII缺失的动物显示出随着pendrin的下调沿着的闰细胞的重塑。另一方面，NCC KO小鼠显示pendrin和ENaC的显著上调。在基线条件下，两种模型均未显示任何显著的盐浪费。我们假设，pendrin的上调是必不可少的，为防止盐浪费在NCC KO mixtes.Methods和ResultsTo测试这一假设，我们产生了NCC/CAII双KO（dKO）小鼠通过交叉与单删除NCC和CAII的小鼠。NCC/CAII dKO小鼠显示pendrin的显著下调，沿着多尿和盐耗。其结果是，dKO小鼠开发的体积消耗，这是与无法浓缩urina.ConclusionsWe的结论是上调pendrin是必不可少的，为防止盐和水浪费NCC缺陷的动物和其下调或失活将导致盐浪费，受损的水保护和体积消耗在设置NCC失活或抑制。
Background and AimsThe thiazide-sensitive Na+-Cl-cotransporter NCC and the Cl-/HCO 3-exchanger pendrin are expressed on apical membranes of distal cortical nephron segments and mediate salt absorption, with pendrin working in tandem with the epithelial Na+ channel (ENaC) and the Na+-dependent chloride/bicarbonate exchanger (NDCBE), whereas NCC is working by itself. A recent study showed that NCC and pendrin compensate for loss of each other under basal conditions, therefore masking the role that each plays in salt reabsorption. Carbonic anhydrase II (CAII, CA2 or CAR2) plays an important role in acid-base transport and salt reabsorption in the proximal convoluted tubule and acid-base transport in the collecting duct. Animals with CAII deletion show remodeling of intercalated cells along with the downregulation of pendrin. NCC KO mice on the other hand show significant upregulation of pendrin and ENaC. Neither model shows any significant salt wasting under baseline conditions. We hypothesized that the up-regulation of pendrin is essential for the prevention of salt wasting in NCC KO mice.Methods and ResultsTo test this hypothesis, we generated NCC/CAII double KO (dKO) mice by crossing mice with single deletion of NCC and CAII. The NCC/CAII dKO mice displayed significant downregulation of pendrin, along with polyuria and salt wasting. As a result, the dKO mice developed volume depletion, which was associated with the inability to concentrate urine.ConclusionsWe conclude that the upregulation of pendrin is essential for the prevention of salt and water wasting in NCC deficient animals and its downregulation or inactivation will result in salt wasting, impaired water conservation and volume depletion in the setting of NCC inactivation or inhibition.