Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure
Calcium-binding proteins annexin A2 and S100A6 are sensors of tubular injury and recovery in acute renal failure
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DOI：
10.1111/j.1523-1755.2005.00740.x
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发表时间：
2005-12-01
影响因子：
19.6
通讯作者：
Chen, A
中科院分区：
文献类型：
--
作者：
Cheng, CW;Rifai, A;Chen, A
背景细胞钙升高与急性肾小管坏死有关，这是急性肾衰竭（ARF）的最常见原因。钙信号在急性肾小管坏死中诱导静止肾小管细胞增殖和分化的机制尚未阐明。通过单次静脉注射硝酸铀酰诱导小鼠急性肾小管坏死，并在1、3、7和14天后进行检查。通过组织学、免疫组织化学、Western印迹、原位杂交和实时逆转录聚合酶链反应（RT-PCR）监测肾功能并评价肾脏。叶酸诱导的ARF和缺血/再灌注（I/R）损伤模型的研究相似。细胞内钙离子和磷脂结合蛋白的mRNA表达分析表明，S100 A6和膜联蛋白A2（Anxa 2）在肾皮质的选择性表达，在第3天显着升高，并在第7天逐渐下降，并在第14天进一步衰减。同样，两种蛋白质的表达，如通过免疫组织化学和Western印迹分析所示，增加，并在第7天达到峰值水平，然后在第14天逐渐下降。波形蛋白是去分化细胞的标志物，在恢复期高度表达。结合原位杂交免疫组化显示S100 A6和Anxa 2与增殖细胞核抗原（PCNA）共定位。在另外两种小鼠急性肾小管坏死模型中，即缺血再灌注损伤和叶酸诱导的ARF中证实了这种现象的普遍性。总的来说，这些研究结果表明，S100 A6和Anxa 2的表达，启动响应肾小管损伤，坚持在急性肾功能衰竭的肾小管细胞的整个恢复过程中平行。
Background. Rise in cellular calcium is associated with acute tubular necrosis, the most common cause of acute renal failure (ARF). The mechanisms that calcium signaling induce in the quiescent tubular cells to proliferate and differentiate during acute tubular necrosis have not been elucidated.Methods. Acute tubular necrosis induced in mice by single intravenous injection of uranyl nitrate and examined after 1, 3, 7, and 14 days. Renal function was monitored and kidneys were evaluated by histology, immunohistochemistry, Western blotting, in situ hybridization, and real-time reverse transcription-polymerase chain reaction (RT-PCR). Models of folic acid induced-ARF and ischemic/reperfusion (I/R) injury were similarly investigated.Results. Analysis of mRNA expression of intracellular calcium and phospholipid-binding proteins demonstrated selective expression of S100A6 and Annexin A2 (Anxa2) in the renal cortex with marked elevation on day 3, and gradually decline on day 7 and further attenuation on day 14. Similarly, the expression of both proteins, as demonstrated by immunohistochemistry and Western blot analysis, was increased and reached the peak level on day 7 and then gradually declined by day 14. Vimentin, a marker of dedifferentiated cells, was highly expressed during the recovery phase. Combined in situ hybridization immunohistochemistry revealed colocalization of both S100A6 and Anxa2 with proliferating cell nuclear antigen ( PCNA). The universality of this phenomenon was confirmed in two other mouse acute tubular necrosis models, the ischemic-reperfusion injury and folic acid-induced ARF.Conclusion. Collectively, these findings demonstrate that S100A6 and Anxa2 expression, initiated in response to tubular injury, persist in parallel throughout the recovery process of tubular cells in acute renal failure.