Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with long-term sequelae, partly due to the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2,950 phosphosites through multi-proteomics analyses. Here we denote the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.

中文翻译：

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败血症诱导的肾损伤的全球蛋白质组和磷酸化蛋白质组格局

脓毒症诱发的急性肾损伤（S-AKI）是住院和重症患者最常见的并发症，其特征是败血症发作后数小时或数天，肾功能迅速下降。据信由微生物感染引起的全身性炎症在免疫受损的条件下导致肾脏损害。然而，尽管AKI已被确认为具有长期后遗症的疾病，部分原因是与之相关的慢性肾脏疾病（CKD）的较高风险，在分子水平上对肾脏病理生理学的理解以及术后动态调节的整体观点S-AKI（包括过渡到CKD）仍然受到限制。S-AKI的现有研究主要集中在从体液中获得败血症生物标志物。在目前的研究中，我们使用盲肠结扎和穿刺（CLP）构建了中度脓毒症小鼠模型，并检查了CLP手术后第2天和第7天肾脏蛋白质组和磷酸化蛋白质组的时间变化，这与S-AKI和向CKD的转化相对应，分别采用超快速和经济的基于过滤器的样品处理方法与无标记定量方法相结合。我们通过多蛋白质组学分析共同鉴定了2119个蛋白质和2950个磷酸位点。在这里，我们表示对S-AKI及其过渡到CKD的特异性反应途径，包括调节细胞代谢调节，氧化应激和患病肾脏的能量消耗。我们的数据可以作为鉴定败血症诱发的肾脏疾病的机制和生物标志物的丰富资源。