WATER CHANNEL EXPRESSION IN HUMAN ADPKD KIDNEYS

WATER CHANNEL EXPRESSION IN HUMAN ADPKD KIDNEYS
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DOI:
10.1152/ajprenal.1995.268.3.f398
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发表时间:
1995-03-01
影响因子:
4.2
通讯作者:
PERRONE, RD
PERRONE, RD
中科院分区:
医学2区
文献类型:
--
作者:
BACHINSKY, DR;SABOLIC, I;PERRONE, RD

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常染色体显性遗传性多囊肾病(ADPKD)的囊肿扩大部分是由于溶质和液体运输到囊肿腔内。在正常肾脏的近端小管和细的降支中,这些节段的高跨上皮水渗透性是由于水通道蛋白水通道蛋白-CHIP(AQP-CHIP,即,AQP-1)。正常肾脏的集合管表达该基因家族的另一个成员,水通道蛋白集合管(AQP-CD,即,AQP-2)。检测了ADPKD和正常人肾脏中这两个水通道蛋白基因家族成员的表达和分布。在这两种组织中,用抗AQP-CHIP抗体进行的Western印迹显示了主要的28-kDa条带。免疫荧光显示,AQP-CHIP在正常和ADPKD肾脏近端小管和Henle氏管的细降支中均有表达。在后者中,AQP-CHIP在71%的囊肿衬里上皮中检测到。许多囊肿近端小管标记物gp 330呈阳性(44%)。一些表达AQP-CHIP的囊肿没有对gp 330染色,这表明一个下降的薄肢起源,少数囊肿对两个标记物都是阴性的。在正常人肾脏中,用抗AQP-CD抗体的Western印迹显示在28 kDa处的条带。AQP-CD定位于集合管,在正常人肾脏中未显示与gp 330的共定位。在ADPKD肾脏中,AQP-CD仅在8%的囊肿中表达。总之,水通道,主要是AQP-CHIP,在上皮细胞中表达,类似于ADPKD肾脏中80%的囊肿。这一发现表明水通道可能在液体进入囊腔中发挥作用。
Cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) results in part from the transport of solute and fluid into the lumen of the cyst. In proximal tubules and thin descending limbs of normal kidneys, the high transepithelial water permeability of these segments is due to the presence of the water channel protein, aquaporin-CHIP (AQP-CHIP, i.e., AQP-1). The collecting ducts of normal kidneys express another member of this gene family, the aquaporin collecting duct (AQP-CD, i.e., AQP-2). The expression and distribution of these two members of the aquaporin gene family were examined in ADPKD and normal human kidneys. In both tissues, Western blotting with the anti-AQP-CHIP antibody revealed a major 28-kDa band. By immunofluorescence, AQP-CHIP was present in proximal tubules and thin descending limbs of Henle of both normal and ADPKD kidneys. In the latter, AQP-CHIP was detected in the epithelia lining 71% of cysts. Many cysts were positive for the proximal tubule marker gp330 (44%). Some cysts expressing AQP-CHIP did not stain for gp330, suggesting a descending thin limb origin, and a few cysts were negative for both markers. In normal human kidney, Western blotting with the anti-AQP-CD antibody revealed a band at 28 kDa. AQP-CD was localized to collecting ducts and did not show colocalization with gp330 in normal human kidney. In ADPKD kidney, AQP-CD was expressed by only 8% of cysts. In summary, water channels, primarily AQP-CHIP, are expressed in epithelial cells Lining cysts in similar to 80% of cysts in ADPKD kidneys. This finding suggests the possibility that water channels could play a role in fluid movement into cyst lumina.