Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.
Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice.
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DOI：
10.1038/ki.2012.223
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发表时间：
2012-10
影响因子：
19.6
通讯作者：
中科院分区：
文献类型：
--
作者：
活性氧、内皮功能障碍、炎症和丝裂原活化蛋白激酶在缺血/再灌注肾损伤的发病机制中起重要作用。斯钙素-1（STC 1）通过诱导线粒体解偶联蛋白抑制许多系统中超氧化物的产生，并阻断苦参碱诱导的内皮通透性升高。在这里，我们测试是否转基因过表达STC 1保护双侧缺血/再灌注肾损伤。野生型小鼠中的这种损伤导致肌酐清除率减半;严重的肾小管空泡化和管型形成;巨噬细胞和T细胞浸润增加;血管通透性更高;超氧化物和过氧化氢的产生更大;以及活化ERK/活化JNK和p38的比率更高，所有这些都与假处理对照组相比。然而，人STC 1表达的转基因小鼠对等同的缺血/再灌注损伤具有抗性，这表明这些参数中的任何一个与对照组相比都没有显著变化。转基因小鼠肾小管上皮细胞表达较高的线粒体解偶联蛋白2和较低的超氧化物生成。用百草枯（一种活性氧生成剂）预处理转基因小鼠，在损伤前恢复了对缺血/再灌注肾损伤的易感性，这表明STC 1通过抗氧化机制提供保护。因此，STC 1可能是缺血/再灌注肾损伤的治疗靶点。
Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated ERK/activated JNK and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury.
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影响因子：
19.6
作者：
Dong, X.;Swaminathan, S.;Griffin, M. D.
通讯作者：
Griffin, M. D.
影响因子：
4.8
作者：
Echtay, KS;Murphy, MP;Brand, MD
通讯作者：
Brand, MD
影响因子：
6.1
作者：
Jo, SK;Sung, SA;Kim, HK
通讯作者：
Kim, HK
DOI：
10.1152/ajprenal.00138.2003
发表时间：
2004-02-01
影响因子：
4.2
作者：
Kanellis, J;Bick, R;Sheikh-Hamad, D
通讯作者：
Sheikh-Hamad, D
影响因子：
19.6
作者：
James, K;Seitelbach, M;Wagner, GF
通讯作者：
Wagner, GF