Soluble urokinase plasminogen activator receptor promotes endoplasmic reticulum stress and apoptosis susceptibility through RAGE in sepsis acute kidney injury

作者：Bingqing Wang, Jiabei Wang, Qi Chen, Chao Gao, Yue Wang, Yujie Zan, Yuwei Tan, Zhenying Wu, Jun Jiang, Jinmeng Suo, Jing Zhang, Zhiyong Peng · 发表于：Molecular Medicine · 年份：2025 · DOI：10.1186/s10020-025-01352-w · 被引用次数：5 · 研究领域：Acute Kidney Injury Research、Chronic Kidney Disease and Diabetes、Dialysis and Renal Disease Management

BACKGROUND: Acute kidney injury (AKI) is a common complication among critically ill patients, associated with an increased risk of adverse outcomes. There is an urgent need for novel biomarkers to assist in the early detection and management of AKI. Soluble urokinase plasminogen activator receptor (suPAR) is an inflammation-related, immune-derived molecule implicated in the pathogenesis of several diseases, including kidney diseases. METHODS: We characterized the ability of serum suPAR levels to diagnose AKI in 124 patients admitted to the intensive care unit (ICU). Additionally, in vivo and in vitro experiments were performed to explore the underlying mechanisms between suPAR and the development of AKI. We stimulated HK-2 cells with suPAR to investigate its effects on HK-2 cells. Additionally, Methods such as receptor inhibitors, protein docking, and co—immunoprecipitation were used to study how suPAR acts on HK-2 cells. We further explored whether the uPAR monoclonal antibody could alleviate acute kidney injury in septic mice. RESULTS: We found that serum suPAR levels were significantly elevated in patients with AKI. In addition, total suPAR/uPAR was elevated in the renal cortex of AKI mice, and serum suPAR levels were also increased. In vitro cell experiments demonstrated that suPAR stimulation promoted endoplasmic reticulum stress (ER stress) and the expression of apoptosis—related proteins in HK-2 cells and increased intracellular reactive oxygen species (ROS). Consisten...