Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease
Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease
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DOI：
10.1152/ajprenal.1996.271.1.f169
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发表时间：
1996-07-01
影响因子：
4.2
通讯作者：
Wilson, PD
中科院分区：
文献类型：
--
作者：
Devuyst, O;Burrow, CR;Wilson, PD
水通道蛋白1（AQP 1）和水通道蛋白2（AQP 2）分别位于近端小管（PT）和Henle氏细支（DTL），是参与水跨肾小管上皮细胞转运的通道。利用抗AQP 1和AQP 2的抗体，我们在此显示了AQP 1和AQP 2在正常人发育和成人肾脏以及常染色体显性多囊肾病（ADPKD）中的表达。与大鼠不同，AQP 1和AQP 2在人类肾发生早期（妊娠12周）表达。AQP 1首先见于发育中的PT上皮细胞，主要在顶端细胞膜，并在15周，也检测到DTL。AQP 2从12周开始在输尿管分支芽和CD系统的顶端细胞膜上表达，并贯穿整个发育过程。在成人正常肾脏中，AQP 1定位于PT和DTL的顶侧和基底侧膜域，而AQP 2仅限于CD的主细胞。AQP 1和AQP 2在早期ADPKD也有这种分布，只是AQP 1主要位于扩张PT的顶膜区。在终末期ADPKD中，三分之二的囊肿表达AQP 1或AQP 2，但这两个水通道从未在同一囊肿中共存。蛋白质印迹分析显示，AQP 1和AQP 2在正常成人肾脏中表达最高，在胎儿肾脏中表达较低，并且随着ADPKD囊性进展程度的降低而降低。这些数据1）证明了AQP 1和AQP 2在人胎儿和成人肾脏中的特异性、互斥定位; 2）表明两种通道在肾发生早期表达; 3）表明定位的互斥性即使在终末期ADPKD中也保持不变。
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.