Altered expression of rat renal cortical OAT1 and OAT3 in response to bilateral ureteral obstruction
Altered expression of rat renal cortical OAT1 and OAT3 in response to bilateral ureteral obstruction
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DOI：
10.1111/j.1523-1755.2005.00741.x
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发表时间：
2005-12-01
影响因子：
19.6
通讯作者：
Torres, AM
中科院分区：
文献类型：
--
作者：
Villar, SR;Brandoni, A;Torres, AM
背景双侧输尿管梗阻（BUO）的特点是血流动力学和肾小管病变的发展。然而，对有机阴离子肾脏转运蛋白的表达知之甚少。本研究旨在研究BUO大鼠肾脏对氨基马尿酸（PAH）的排泄及肾皮质有机阴离子转运蛋白1（OAT 1）和有机阴离子转运蛋白3（OAT 3）的表达。雄性Wistar大鼠行双侧输尿管近端梗阻24小时（BUO）或假手术。输尿管释放24小时后，进行以下研究：使用常规清除技术进行PAH肾排泄，使用免疫印迹和免疫细胞化学技术（光镜和共聚焦免疫荧光显微镜分析）进行OAT 1和OAT 3丰度（来自肾皮质的匀浆、细胞内和基底外侧质膜组分）。BUO大鼠的PAH肾脏排泄量较低。在阻塞的肾脏中，免疫印迹显示肾皮质基底外侧质膜中OAT 1和OAT 3的丰度显著降低。与假手术组相比，在BUO大鼠肾脏的匀浆和细胞内膜组分中观察到OAT 1表达增加，表明该载体的内化。免疫细胞化学技术证实了这些结果。相反，梗阻肾组织匀浆和细胞内膜OAT3表达均降低。BUO与近端小管细胞基底侧质膜中OAT 1和OAT 3的下调相关，因此这些载体可能在梗阻肾中显示的受损的有机阴离子排泄中发挥重要作用。
Background. Bilateral ureteral obstruction (BUO) is characterized by the development of hemodynamic and tubular lesions. However, little is known about the expression of organic anion renal transporters. The objective of this work was to study the renal excretion of p-aminohippurate (PAH) and the cortical renal expression of the organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) in BUO rats.Methods. Male Wistar rats underwent bilateral obstruction of the proximal ureters for 24 hours (BUO) or sham operation. After 24 hours of ureteral releasing, the following studies were performed: PAH renal excretion employing conventional clearance techniques and OAT1 and OAT3 abundance (homogenates, intracellular and basolateral plasma membrane fractions from renal cortex) using immunoblotting and immunocytochemical techniques (light microscopic and confocal immunofluorescence microscopic analysis).Results. BUO rats showed a lower renal excretion of PAH. In obstructed kidneys, immunoblotting revealed a significant decrease in the abundance of both OAT1 and OAT3 in basolateral plasma membranes from renal cortex. An increase of OAT1 expression was observed in homogenates and in intracellular membrane fractions in kidneys from BUO rats compared with sham-operated ones, indicating an internalization of this carrier. Immunocytochemical techniques confirmed these results. On the contrary, OAT3 expression was reduced both in homogenates and in intracellular membrane fractions in obstructed kidneys.Conclusion. BUO was associated with down-regulation of OAT1 and OAT3 in basolateral plasma membranes from proximal tubule cells, thus these carriers may play important roles in the impaired organic anion excretion displayed in the obstructed kidney.