ABC transporter expression profiling after ischemic reperfusion injury in mouse kidney
ABC transporter expression profiling after ischemic reperfusion injury in mouse kidney
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DOI：
10.1038/sj.ki.5000407
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发表时间：
2006-06-01
影响因子：
19.6
通讯作者：
Masereeuw, R.
中科院分区：
文献类型：
--
作者：
Huls, M.;van den Heuvel, J. J. M. W.;Masereeuw, R.
肾脏ATP结合盒（ABC）转运蛋白在清除代谢废物和体内异物中具有重要作用。肾脏有能力严格控制这些外排转运蛋白的表达，以维持体内平衡，并作为适应环境应激的主要机制。在本研究中，我们研究了基础条件下，诱导缺血后和再生后小鼠肾脏中45个ABC转运蛋白基因的表达。钳夹后两天，小鼠显示肾肌酐清除率降低76%，在7天内明显改善。这通过组织学检查得到证实。缺血后7天，实时定量聚合酶链反应数据显示，abcb1，abcb11和abcc4的转录丰度增加，而abca3，abcc2和abcg2的转录丰度减少。14天后，所有转运蛋白的表达均恢复至基线，但abcb 11除外，其表达减少。Abcb11是肝小管主要的胆盐输出泵。在这里，我们首次显示在肾脏中的表达和定位的转运近端小管的顶膜。另一种新的肾脏转运蛋白，abca 3的存在，证实了蛋白质印迹。免疫组化显示abca 3定位于肾小管周毛细血管和近曲小管顶膜。总之，在诱导肾脏缺血再灌注损伤后，ABC转运蛋白似乎受到差异调节，这可能与肾脏再生过程有关。此外，我们首次发现了abcb11和abca3在小鼠肾脏中的表达和亚细胞定位。
Renal ATP binding cassette (ABC) transporters have an important role in the elimination of metabolic waste products and compounds foreign to the body. The kidney has the ability to tightly control the expression of these efflux transporters to maintain homeostasis, and as a major mechanism of adaptation to environmental stress. In the present study, we investigated the expression of 45 ABC transporter genes in the mouse kidney under basal conditions, after induction of ischemia and after regeneration. Two days after clamping, mice showed a 76% decrease in renal creatinine clearance, which improved clearly within 7 days. This was confirmed by histological examinations. Seven days after ischemia, real-time quantitative Polymerase chain reaction data showed that transcript abundance of abcb1, abcb11, and abcc4 was increased, and that of abca3, abcc2, and abcg2 decreased. Expression of all transporters returned to baseline after 14 days, except for abcb11, which was reduced. Abcb11 is the major liver canalicular bile salt export pump. Here we show for the first time expression in the kidney and localization of the transporter to the apical membrane of proximal tubules. The presence of another novel renal transporter, abca3, was confirmed by Western blotting. Immunohistochemistry showed that abca3 is localized to the peritubular capillaries and apical membrane of proximal tubules. In conclusion, after inducing ischemic reperfusion injury in the kidney, ABC transporters appear to be differentially regulated, which might be associated with the renal regeneration process. Furthermore, we showed for the first time expression and subcellular localization of abcb11 and abca3 in mouse kidney.