Pu Mengmeng, Zhao Huanhuan, Xu Silei, Gu Xiaohui, Feng Qiang, Huang Peng
Department of Nephrology, Xingtai People's Hospital, Xingtai, China.
Department of Nephrology, Jinan Weigao Nephrology Hospital, Jinan, China.
Nephron. 2025;149(4):197-206. doi: 10.1159/000541348. Epub 2024 Nov 15.
Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis. miR-340-5p has been identified as an effective biomarker of various human diseases. As the downstream target, the involvement of lysine (K)-specific demethylase 4C (KDM4C) in SA-AKI would help interpret the regulatory mechanism of miR-340-5p. The significance of miR-340-5p in the onset and progression of SA-AKI was evaluated to provide a potential therapeutic target for SA-AKI.
This study enrolled 64 healthy individuals (control) and 159 sepsis patients (92 SA-AKI and 67 non-AKI) and collected urine samples. The urine level of miR-340-5p was analyzed by PCR, and a series of statistical analyses were conducted to assess the clinical significance of miR-340-5p in the occurrence and development of SA-AKI. The injured renal tubular epithelial cells were established with LPS induction. The roles of miR-340-5p in cellular processes were evaluated.
Increasing urine miR-340-5p discriminated SA-AKI patients from healthy individuals (AUC = 0.934) and non-AKI sepsis patients (AUC = 0.806) sensitively. Additionally, elevated miR-340-5p could predict the adverse prognosis (HR = 5.128, 95% CI = 1.259-20.892) and malignant development of SA-AKI patients. In vitro, lipopolysaccharide (LPS) also induced an increased level of miR-340-5p and significant cell injury in the renal tubular epithelial cell; silencing miR-340-5p could alleviate the suppressed proliferation, migration, and invasion caused by LPS. In mechanism, miR-340-5p negatively regulated KDM4C, which mediated the function of miR-340-5p.
miR-340-5p served as a diagnostic and prognostic biomarker of SA-AKI and regulated renal tubular epithelial cell injury via modulating KDM4C.
脓毒症相关急性肾损伤（SA-AKI）是脓毒症常见的并发症。miR-340-5p已被确定为多种人类疾病的有效生物标志物。作为下游靶点，赖氨酸（K）特异性去甲基化酶4C（KDM4C）参与SA-AKI有助于阐释miR-340-5p的调控机制。本研究评估了miR-340-5p在SA-AKI发病及进展中的意义，以期为SA-AKI提供潜在的治疗靶点。
本研究纳入64名健康个体（对照组）和159名脓毒症患者（92例SA-AKI患者和67例非AKI患者），并收集尿液样本。采用聚合酶链反应（PCR）分析尿液中miR-340-5p水平，并进行一系列统计分析，以评估miR-340-5p在SA-AKI发生发展中的临床意义。通过脂多糖（LPS）诱导建立受损肾小管上皮细胞模型，评估miR-340-5p在细胞过程中的作用。
尿液中miR-340-5p水平升高可灵敏地区分SA-AKI患者与健康个体（曲线下面积[AUC]=0.934）以及非AKI脓毒症患者（AUC=0.806）。此外，miR-340-5p升高可预测SA-AKI患者的不良预后（风险比[HR]=5.128，95%置信区间[CI]=1.259-20.892）及病情恶化。在体外，脂多糖（LPS）也可诱导肾小管上皮细胞中miR-340-5p水平升高及明显的细胞损伤；沉默miR-340-5p可减轻LPS所致的细胞增殖、迁移及侵袭抑制。机制上，miR-340-5p负向调控KDM4C，后者介导miR-340-5p的功能。
miR-340-5p作为SA-AKI的诊断及预后生物标志物，通过调节KDM4C调控肾小管上皮细胞损伤。
