Acute Kidney Injury (AKI) is a frequent complication of sepsis and an important cause of morbidity and mortality worldwide. A cornerstone of sepsis-associated acute kidney injury (SA-AKI) is dysregulated inflammation leading to increased tissue oxidative stress and free radical formation which leads to multiple forms of cell death. DJ-1 is a peroxiredoxin protein with multiple functions including its ability to control cellular oxidative stress. Although DJ-1 is expressed prominently by renal tubules, its role in AKI has not been investigated. In this study we examined the effect of DJ-1 deficiency in a murine model of endotoxin-induced AKI. Endotoxemia induced greater kidney injury in DJ-1-deficient mice. Further, DJ-1 deficiency increased renal oxidative stress associated with increased renal tubular apoptosis and with expression of death domain-associated protein (DAXX). Similar to the in vivo model, in vitro studies, using a medullary collecting duct cell line (IMCD3) and cytotoxic serum, we show that serum obtained from WT mice results in increased expression of s100A8/s100A9, DAXX, and apoptosis in DJ-1 deficient iMCD3 cells. Our findings demonstrate a novel renal protective role for renal tubular DJ-1 during endotoxemia through control of oxidative stress, renal inflammation, and DAXX-dependent apoptosis.

中文翻译：

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DJ-1在内毒素诱导的急性肾损伤中的保护作用。

急性肾损伤 (AKI) 是脓毒症的常见并发症，也是全球发病率和死亡率的重要原因。脓毒症相关急性肾损伤 (SA-AKI) 的基石是失调的炎症，导致组织氧化应激和自由基形成增加，从而导致多种形式的细胞死亡。DJ-1 是一种过氧化物酶蛋白，具有多种功能，包括控制细胞氧化应激的能力。尽管 DJ-1 主要由肾小管表达，但尚未研究其在 AKI 中的作用。在这项研究中，我们检测了 DJ-1 缺乏对内毒素诱导的 AKI 小鼠模型的影响。内毒素血症在 DJ-1 缺陷小鼠中引起更大的肾损伤。更远，DJ-1 缺乏增加了与肾小管凋亡增加和死亡域相关蛋白 (DAXX) 表达相关的肾脏氧化应激。与体内模型相似，体外研究使用髓质集合管细胞系 (IMCD3) 和细胞毒性血清，我们显示从 WT 小鼠获得的血清导致 DJ-1 中 s100A8/s100A9、DAXX 和细胞凋亡的表达增加缺乏 iMCD3 细胞。我们的研究结果表明，通过控制氧化应激、肾脏炎症和 DAXX 依赖性细胞凋亡，在内毒素血症期间肾小管 DJ-1 具有新的肾脏保护作用。和 DJ-1 缺陷型 iMCD3 细胞的凋亡。我们的研究结果表明，通过控制氧化应激、肾脏炎症和 DAXX 依赖性细胞凋亡，在内毒素血症期间肾小管 DJ-1 具有新的肾脏保护作用。和 DJ-1 缺陷型 iMCD3 细胞的凋亡。我们的研究结果表明，通过控制氧化应激、肾脏炎症和 DAXX 依赖性细胞凋亡，在内毒素血症期间肾小管 DJ-1 具有新的肾脏保护作用。