Developmental expression of sodium entry pathways in rat nephron

Developmental expression of sodium entry pathways in rat nephron
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DOI:
10.1152/ajprenal.1999.276.3.f367
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发表时间:
1999-03-01
影响因子:
4.2
通讯作者:
Bachmann, S
Bachmann, S
中科院分区:
医学2区
文献类型:
--
作者:
Schmitt, R;Ellison, DH;Bachmann, S

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在过去的几年中,已经描述了成人肾小管中离子转运蛋白的表达位点,并将其与功能特性相关联。关于肾小管形态发生过程中表达位点的信息较少,尽管这种表达模式可能对肾脏发育至关重要。在目前的研究中,通过绘制大鼠肾发生过程中钠转运途径的表达来定义肾轴分化的模式。采用原位杂交和免疫组织化学相结合的方法定位 Na-P-i 协同转运蛋白 2 型 (NaPi2)、布美他尼敏感的 Na-K-2Cl 协同转运蛋白 (NKCC2)、噻嗪类敏感的 Na-Cl 协同转运蛋白 (NCC)、Na/Ca 交换器 (NaCa)、上皮钠通道 (rENaC)、 和 11 β-羟基类固醇脱氢酶 (11HSD)。这些蛋白质的表达开始于后S形阶段。 NKCC2 最初在致密斑区域表达,后来延伸到新生的亨利袢升肢 (TAL),而当探测 NaPi2 时,亨利袢的近端管状部分的分化表现出相对延迟的起始。 NCC 最初发现于新生远曲小管 (DCT) 的远端,后来延伸至与 TAL 的交界处。经过一段时间的比例变化后,DCT 明显细分为仅表达 NCC 的近端部分和与 NaCa 一起表达 NCC 的远端部分。在早期新生连接小管 (CNT) 和集合管中以及随后在 DCT 的远端部分中观察到 rENaC 和 11HSD 的强共表达。晚期远端回旋中 NCC、NaCa、11HSD 和 rENaC 表达的个体发育表明 CNT 的异质起源。这些数据详细分析了发育中肾小管的解剖分化与肾小管转运蛋白表达之间的关系。
During the past several years, sites of expression of ion transport proteins in tubules from adult kidneys have been described and correlated with functional properties. Less information is available concerning sites of expression during tubule morphogenesis, although such expression patterns may be crucial to renal development. In the current studies, patterns of renal axial differentiation were defined by mapping the expression of sodium transport pathways during nephrogenesis in the rat. Combined in situ hybridization and immunohistochemistry were used to localize the Na-P-i cotransporter type 2 (NaPi2), the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2), the thiazide-sensitive Na-Cl cotransporter (NCC), the Na/Ca exchanger (NaCa), the epithelial sodium channel (rENaC), and 11 beta-hydroxysteroid dehydrogenase (11HSD). The onset of expression of these proteins began in post-S-shape stages. NKCC2 was initially expressed at the macula densa region and later extended into the nascent ascending limb of the loop of Henle (TAL), whereas differentiation of the proximal tubular part of the loop of Henle showed a comparatively retarded onset when probed for NaPi2. The NCC was initially found at the distal end of the nascent distal convoluted tubule (DCT) and later extended toward the junction with the TAL. After a period of changing proportions, subsegmentation of the DCT into a proximal part expressing NCC alone and a distal part expressing NCC together with NaCa was evident. Strong coexpression of rENaC and 11HSD was observed in early nascent connecting tubule (CNT) and collecting ducts and later also in the distal portion of the DCT. Ontogeny of the expression of NCC, NaCa, 11HSD, and rENaC in the late distal convolutions indicates a heterogenous origin of the CNT. These data present a detailed analysis of the relations between the anatomic differentiation of the developing renal tubule and the expression of tubular transport proteins.