Important role of apoptosis signal-regulating kinase 1 in ischemic acute kidney injury
Important role of apoptosis signal-regulating kinase 1 in ischemic acute kidney injury
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DOI：
10.1016/j.bbrc.2007.10.122
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发表时间：
2007-12-28
影响因子：
3.1
通讯作者：
Sasaki, Sel
中科院分区：
文献类型：
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作者：
Terada, Yoshio;Inoshita, Seiji;Sasaki, Sel
我们研究了凋亡信号调节激酶1（ASK 1）在缺血/再灌注（I/R）诱导的急性肾损伤（阿基）中的作用。I/R损伤后，ASK 1 +/+小鼠的血尿素氮（BUN）和血清肌酐显著高于ASK 1-/-小鼠。ASK 1 +/+小鼠的肾组织学显示显著更大的肾小管坏死和降解。在ASK 1-/-小鼠中，I/R损伤后ASK 1、JNK和p38 K的磷酸化以及TUNEL阳性细胞和浸润的白细胞数量减少。缺氧条件下培养的ASK 1-/-小鼠肾小管上皮细胞（TECs）凋亡率明显降低。显性活性的ASK 1转染诱导TEC凋亡。单核细胞趋化蛋白-1（MCP-1）的蛋白表达在I/R损伤后ASK 1-/-小鼠中显著减弱。显性负性ASK 1转染显著降低TEC中MCP-1的产生。这些结果表明，ASK 1在I/R诱导的阿基中被激活，并且ASK 1的阻断减弱肾小管凋亡、MCP-1表达和肾功能。(C)2007爱思唯尔公司All rights reserved.
We investigated the role of apoptosis signal-regulating kinase 1 (ASK1) in ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). Blood urea nitrogen (BUN) and serum creatinine were significantly higher in ASK1+/+ mice than in ASK1-/- mice after I/R injury. Renal histology of ASK1+/+ mice showed significantly greater tubular necrosis and degradation. In ASK1-/- mice, phosphorylation of ASK1, JNK, and p38K, and the number of TUNEL-positive cells and infiltrated leukocytes decreased after I/R injury. Apoptotic changes were significantly decreased in cultured renal tubular epithelial cells (TECs) from ASK1-/- mice under hypoxic condition. Transfection with dominant-active ASK1 induced apoptosis in TECs. Protein expression of monocyte chemoattractant protein-1 (MCP-1) was significantly weaker in ASK1-/- mice after I/R injury. Transfection with dominant negative-ASK1 significantly decreased MCP-1 production in TECs. These results demonstrated that ASK1 is activated in I/R-induced AKI, and blockage of ASK1 attenuates renal tubular apoptosis, MCP-1 expression, and renal function. (C) 2007 Elsevier Inc. All rights reserved.