Huls M, van den Heuvel J J M W, Dijkman H B P M, Russel F G M, Masereeuw R
Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Kidney Int. 2006 Jun;69(12):2186-93. doi: 10.1038/sj.ki.5000407. Epub 2006 Apr 12.
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.
肾ATP结合盒(ABC)转运蛋白在清除代谢废物和外来化合物方面发挥着重要作用。肾脏能够严格控制这些外排转运蛋白的表达以维持体内平衡,这也是适应环境应激的主要机制。在本研究中,我们调查了45种ABC转运蛋白基因在小鼠肾脏基础状态下、缺血诱导后及再生后的表达情况。夹闭后两天,小鼠的肾肌酐清除率下降了76%,但在7天内明显改善。组织学检查证实了这一点。缺血7天后,实时定量聚合酶链反应数据显示,abcb1、abcb11和abcc4的转录本丰度增加,而abca3、abcc2和abcg2的转录本丰度下降。14天后,除abcb11表达降低外,所有转运蛋白的表达均恢复至基线水平。Abcb11是主要的肝小管胆汁盐输出泵。在此我们首次展示了其在肾脏中的表达以及该转运蛋白在近端小管顶膜的定位。通过蛋白质印迹法证实了另一种新型肾转运蛋白abca3的存在。免疫组织化学显示abca3定位于近端小管的周毛细血管和顶膜。总之,在诱导肾脏缺血再灌注损伤后,ABC转运蛋白似乎受到不同程度的调节,这可能与肾脏再生过程有关。此外,我们首次展示了abcb11和abca3在小鼠肾脏中的表达及亚细胞定位。