CLONING AND REGULATION OF EXPRESSION OF THE RAT-KIDNEY UREA TRANSPORTER (RUT2)
CLONING AND REGULATION OF EXPRESSION OF THE RAT-KIDNEY UREA TRANSPORTER (RUT2)
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DOI：
10.1172/jci118194
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发表时间：
1995-09-01
影响因子：
15.9
通讯作者：
HEDIGER, MA
中科院分区：
文献类型：
--
作者：
SMITH, CP;LEE, WS;HEDIGER, MA
在哺乳动物中，尿素是氮代谢的主要终产物，在尿液浓缩机制中发挥着核心作用。肾髓质中的尿素积累对于肾脏将尿液浓缩至渗透压高于全身血浆的能力至关重要。肾髓质中尿素排泄和积累的调节取决于专门的根皮素敏感尿素转运蛋白的功能状态。为了研究这些转运蛋白及其表达调节，我们分离了编码兔 UT2 的大鼠同源物 (rUT2) 的 cDNA (You, G., C. P. Smith, Y. Kanai, W.-S. Lee, M. Stelzner, and M. A. Hediger, et al. Nature (Lond.). 1993, 365:844-847)。大鼠 UT2 与兔 UT2 具有 88% 的氨基酸序列同一性，与最近克隆的人红细胞尿素转运蛋白 HUT11 具有 64% 的同一性（Olives, B.、P. Neav、P. Badly、M. A. Hediger、G. Rousselet、J. P. Cartron 和 P. Ripoch J. Biol. Chem. 1994。 269:31649-31652）。对大鼠肾脏 mRNA 的分析揭示了大小为 2.9 和 4.0 kb 的两个转录物，它们具有空间上不同的分布。 Northern 分析和原位杂交表明，4.0-kb 转录本主要对饮食中蛋白质含量的变化做出反应，而 2.9-kb 转录本对动物水合状态的变化做出反应。这些研究表明，两个 rUT2 转录本的表达水平受到不同途径的调节，从而可以独立调节体液和氮平衡。我们的数据为肾尿素转运蛋白 UT2 的调节提供了重要的见解，并为完善我们对尿液浓缩机制及其调节的理解提供了基础。
In mammals, urea is the predominant end-product of nitrogen metabolism and plays a central role in the urinary-concentrating mechanism. Urea accumulation in the renal medulla is critical to the ability of the kidney to concentrate urine to an osmolality greater than systemic plasma. Regulation of urea excretion and accumulation in the renal medulla depends on the functional state of specialized phloretin-sensitive urea transporters. To study these transporters and their regulation of expression we isolated a cDNA which encodes the rat homologue (rUT2) of rabbit UT2 (You, G., C. P. Smith, Y. Kanai, W.-S. Lee, M. Stelzner, and M. A. Hediger, et al. Nature (Lond.). 1993, 365:844-847). Rat UT2 has 88% amino acid sequence identity to rabbit UT2 and 64% identity to the recently cloned human erythrocyte urea transporter, HUT11 (Olives, B., P. Neav, P. Badly, M. A. Hediger, G. Rousselet, J. P. Cartron, and P. Ripoch J. Biol. Chem. 1994. 269:31649-31652). Analysis of rat kidney mRNA revealed two transcripts of size 2.9 and 4.0 kb which had spatially distinct distributions. Northern analysis and in situ hybridization showed that the 4.0-kb transcript was primarily responsive to changes in the protein content of the diet whereas the 2.9-kb transcript was responsive to changes in the hydration state of the animal. These studies reveal that the expression levels of the two rUT2 transcripts are modulated by different pathways to allow fluid and nitrogen balance to be regulated independently. Our data provide important insights into the regulation of the renal urea transporter UT2 and provide a basis on which to refine our understanding of the urinary concentrating mechanism and its regulation.