Devuyst O, Burrow C R, Smith B L, Agre P, Knepper M A, Wilson P D
Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore 21205, USA.
Am J Physiol. 1996 Jul;271(1 Pt 2):F169-83. doi: 10.1152/ajprenal.1996.271.1.F169.
Aquaporin-1 (AQP1), located in proximal tubules (PT) and descending thin limbs of Henle (DTL), and aquaporin-2 (AQP2), located in collecting ducts (CD), are channels involved in water transport across renal tubule epithelia. Using antibodies against AQP1 and AQP2, we here show expression of AQP1 and AQP2 in normal human developing and adult kidneys and in autosomal dominant polycystic kidney disease (ADPKD). Unlike in rats, AQP1 and AQP2 are expressed early during human nephrogenesis (12-wk gestation). AQP1 was first seen in developing PT epithelia, predominantly in apical cell membranes, and, at 15 wk, was also detected in DTL. AQP2 was seen in apical cell membranes of the branching ureteric bud and CD system from 12 wk and throughout development. In adult normal kidneys, AQP1 was localized to apical and basolateral membrane domains of PT and DTL, whereas AQP2 was restricted to principal cells of CD. This distribution of AQP1 and AQP2 was also seen in early stage ADPKD, except that AQP1 was mostly located in the apical membrane region of expanded PT. In end-stage ADPKD, two-thirds of the cysts expressed either AQP1 or AQP2, but these two water channels were never colocalized in the same cyst. Western blot analysis showed maximal expression of AQP1 and AQP2 in normal adult kidneys, lower levels in fetal kidneys, and decreases associated with degree of cystic progression in ADPKD. These data 1) demonstrate specific, mutually exclusive localization of AQP1 and AQP2 in human fetal and adult kidneys; 2) show that both channels are expressed early during nephrogenesis; and 3) show that the mutual exclusivity of localization is maintained even into end-stage ADPKD.
水通道蛋白-1（AQP1）位于近端小管（PT）和髓袢降支细段（DTL），水通道蛋白-2（AQP2）位于集合管（CD），它们是参与水跨肾小管上皮运输的通道。我们使用抗AQP1和AQP2抗体，在此展示了AQP1和AQP2在正常人类发育中和成年肾脏以及常染色体显性多囊肾病（ADPKD）中的表达情况。与大鼠不同，AQP1和AQP2在人类肾发生早期（妊娠12周）就已表达。AQP1最早出现在发育中的PT上皮细胞中，主要位于顶端细胞膜，在15周时，在DTL中也被检测到。AQP2从12周起在分支输尿管芽和CD系统的顶端细胞膜中可见，并贯穿整个发育过程。在成年正常肾脏中，AQP1定位于PT和DTL的顶端和基底外侧膜结构域，而AQP2局限于CD的主细胞。在ADPKD早期也观察到了AQP1和AQP2的这种分布，只是AQP1大多位于扩张的PT的顶端膜区域。在ADPKD终末期，三分之二的囊肿表达AQP1或AQP2，但这两种水通道蛋白从未在同一个囊肿中共定位。蛋白质印迹分析显示，AQP1和AQP2在正常成年肾脏中表达最高，在胎儿肾脏中表达水平较低，且在ADPKD中与囊肿进展程度相关的表达下降。这些数据1）证明了AQP1和AQP2在人类胎儿和成年肾脏中具有特异性、相互排斥的定位；2）表明这两种通道在肾发生早期就已表达；3）表明即使到ADPKD终末期，定位的相互排斥性仍得以维持。
