机构：[1]Department of Critical Care Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.临床科室重症医学科河北医科大学第四医院[2]Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, China.[3]Department of Anesthesiology and Intensive Care Unit, The Second Hospital of Hebei Medical University, Shijiazhuang, China.[4]Intensive Care Unit of Emergency Department, Neurology Branch of Cangzhou Central Hospital, Cangzhou, China.
Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis and greatly increases patient mortality. Recombinant human Klotho protein (Klotho) is a protective protein that can be secreted by the kidney. The aim of this study was to explore the protective effect of Klotho on SA-AKI and its molecular mechanism.In vivo, a mouse SA-AKI model was constructed by cecum ligation perforation (CLP). In vitro, a human renal tubular cell epithelial cell line (HK2) was induced with lipopolysaccharide (LPS) in the SA-AKI model. Determine renal injury markers, inflammatory factors, oxidative stress and molecular proteins related to the ferroptosis signaling pathway.Klotho reduced the release of renal injury markers and inflammatory cytokines, decreased oxidative stress, improved renal histopathological changes, ameliorated mitochondrial damage in mouse renal tubular epithelial cells, increased HK2 cell viability and reduced reactive oxygen species (ROS) accumulation. Exogenous supplementation with Klotho increased the Klotho content in circulating blood, renal tissue and HK2 cells.In the SA-AKI model, Klotho attenuated renal tissue injury, increased HK2 cell viability, decreased inflammatory factor expression and oxidative stress, restored tubular epithelial mitochondrial function, and increased its level in circulating blood, renal tissue and HK2 cells. Klotho probably exerts its protective effects by activating Nrf2 to inhibit the ferroptosis signaling pathway.2023 Translational Andrology and Urology. All rights reserved.
基金：
This work was supported by the Department of Science and Technology of Hebei Province of China (No. 20277707D).
第一作者机构：[1]Department of Critical Care Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
通讯作者：
通讯机构：[1]Department of Critical Care Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.[2]Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, China.[*1]Department of Critical Care Medicine, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang 050011, China[*2]Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, China
推荐引用方式(GB/T 7714)：
Zhou Pan,Zhao Congcong,Chen Yuhong,et al.Klotho activation of Nrf2 inhibits the ferroptosis signaling pathway to ameliorate sepsis-associated acute kidney injury[J].TRANSLATIONAL ANDROLOGY AND UROLOGY.2023,12(12):1871-1884.doi:10.21037/tau-23-573.
APA：
Zhou Pan,Zhao Congcong,Chen Yuhong,Liu Xuefang,Wu Chunxue&Hu Zhenjie.(2023).Klotho activation of Nrf2 inhibits the ferroptosis signaling pathway to ameliorate sepsis-associated acute kidney injury.TRANSLATIONAL ANDROLOGY AND UROLOGY,12,(12)
MLA：
Zhou Pan,et al."Klotho activation of Nrf2 inhibits the ferroptosis signaling pathway to ameliorate sepsis-associated acute kidney injury".TRANSLATIONAL ANDROLOGY AND UROLOGY 12..12(2023):1871-1884
