Zhao Yuhong, Li Yuan, Su Mei, Cai Xiaoyue
Department of Nephrology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China.
Department of Urology, The Third People's Hospital of Yibin, Yibin, China.
Cent Eur J Immunol. 2024;49(4):383-392. doi: 10.5114/ceji.2024.145730. Epub 2024 Dec 11.
Acute kidney injury (AKI) is a common complication of sepsis, characterized by sharply declining renal function. As a global concern, understanding its pathogenesis and improving diagnosis and therapy face significant challenges. MicroRNAs are involved in the progression of a variety of diseases.This research was focused on differences in expression and clinical predictive value of miR-582-5p in sepsis-induced AKI.
Blood and urine samples were collected from 180 patients. Sepsis-induced AKI was imitated in vitro by human kidney 2 (HK2) cells treated with 10 µg/ml lipopolysaccharide (LPS). The relative expression of miR-582-5p and HMGB2 in different conditions was quantified by qRT-PCR. Regulation of gene expression was performed by cell transfection. Cell viability and apoptosis were detected subsequently. Kidney injury and inflammatory assessment were analyzed by means of ELISA. Estimation of oxidative stress was performed using the corresponding kit. The dual luciferase reporter system verified the targeting relationship between miR-582-5p and HMGB2.
Relative expression of miR-582-5p was lower in sepsis patients who suffered AKI later, along with LPS-induced HK2 cells. Both weak viability and elevated apoptosis were reversed by up-regulated miR-582-5p in HK2 cells exposed to LPS. In addition, the concentration of inflammatory factors and oxidation levels showed a significant decrease, based on up-regulated miR-582-5p. The clinical predictive value of miR-582-5p was visualized by a ROC curve with high sensitivity and specificity.
Up-regulated miR-582-5p reduced sepsis-induced AKI, and HMGB2 was a potential downstream target of miR-582-5p.
急性肾损伤（AKI）是脓毒症的常见并发症，其特征是肾功能急剧下降。作为一个全球性问题，了解其发病机制以及改善诊断和治疗面临重大挑战。微小RNA参与多种疾病的进展。本研究聚焦于脓毒症诱导的急性肾损伤中miR-582-5p的表达差异及临床预测价值。
收集180例患者的血液和尿液样本。用10μg/ml脂多糖（LPS）处理人肾2（HK2）细胞，在体外模拟脓毒症诱导的急性肾损伤。通过qRT-PCR定量不同条件下miR-582-5p和HMGB2的相对表达。通过细胞转染进行基因表达调控。随后检测细胞活力和凋亡情况。通过ELISA分析肾损伤和炎症评估。使用相应试剂盒进行氧化应激评估。双荧光素酶报告系统验证miR-582-5p与HMGB2之间的靶向关系。
后期发生急性肾损伤的脓毒症患者以及LPS诱导的HK2细胞中，miR-582-5p的相对表达较低。在暴露于LPS的HK2细胞中，上调miR-582-5p可逆转细胞活力减弱和凋亡增加的情况。此外，基于上调的miR-582-5p，炎症因子浓度和氧化水平显著降低。miR-582-5p的临床预测价值通过具有高敏感性和特异性的ROC曲线得以体现。
上调miR-582-5p可减轻脓毒症诱导的急性肾损伤，且HMGB2是miR-582-5p潜在的下游靶点。
