Liu Xuelan, Zhu Na, Zhang Bo, Xu Shao Bo
Department of Emergency, Ningbo Medical Center Li Huili Hospital, Ningbo, China.
Front Physiol. 2020 Jun 18;11:622. doi: 10.3389/fphys.2020.00622. eCollection 2020.
Acute kidney injury (AKI) is a common and serious complication of sepsis accompanied by kidney dysfunction resulting from various etiologies and pathophysiological processes. Unfortunately, there is currently no ideal therapeutic strategy for AKI. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) play important regulatory roles in the pathogenesis of sepsis-associated AKI. In this study, lncRNA TCONS_00016406 (termed lncRNA 6406), a novel lncRNA identified by using TargetScan, was significantly downregulated in the kidney tissues of mice with sepsis-associated AKI. This study aimed to explore the role of lncRNA 6406 in lipopolysaccharide (LPS)-induced AKI and its potential molecular mechanism. The models of sepsis-induced AKI (called LPS-induced AKI models) in mice and cell lines were established with male C57BL/6 mice and renal tubular epithelial (PTEC) cells, respectively. Twenty-four hours after LPS administration, kidneys and cell samples were collected after various treatments to examine the alterations in the lncRNA 6406 levels and to evaluate the effects on LPS-induced inflammation, oxidative stress, and apoptosis through real-time PCR (RT-PCR) analysis, western blotting, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. The results revealed that lncRNA 6406 could significantly attenuate LPS-induced AKI, as shown by the alleviation of inflammation, the suppression of oxidative stress and the inhibition of apoptosis. Mechanistically, a luciferase reporter assay and additional research showed that lncRNA 6406 functioned as a ceRNA to sponge miRNA-687, thereby modulating LPS-stimulated AKI by targeting the miR-687/PTEN axis; thus, this study presents a novel therapeutic strategy or sepsis-associated AKI.
急性肾损伤（AKI）是脓毒症常见且严重的并发症，伴有由各种病因和病理生理过程导致的肾功能障碍。不幸的是，目前尚无针对AKI的理想治疗策略。大量研究证实，长链非编码RNA（lncRNA）在脓毒症相关性AKI的发病机制中发挥重要调节作用。在本研究中，通过TargetScan鉴定出的一种新型lncRNA——lncRNA TCONS_00016406（称为lncRNA 6406），在脓毒症相关性AKI小鼠的肾组织中显著下调。本研究旨在探讨lncRNA 6406在脂多糖（LPS）诱导的AKI中的作用及其潜在分子机制。分别以雄性C57BL/6小鼠和肾小管上皮（PTEC）细胞建立了小鼠脓毒症诱导的AKI模型（称为LPS诱导的AKI模型）和细胞系模型。给予LPS 24小时后，在各种处理后收集肾脏和细胞样本，通过实时荧光定量聚合酶链反应（RT-PCR）分析、蛋白质印迹法和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色检测lncRNA 6406水平的变化，并评估其对LPS诱导的炎症、氧化应激和细胞凋亡的影响。结果显示，lncRNA 6406可显著减轻LPS诱导的AKI，表现为炎症减轻、氧化应激受到抑制以及细胞凋亡受到抑制。机制上，荧光素酶报告基因检测及其他研究表明，lncRNA 6406作为竞争性内源RNA（ceRNA）吸附miRNA-687，从而通过靶向miR-687/PTEN轴调节LPS刺激的AKI；因此，本研究提出了一种针对脓毒症相关性AKI的新型治疗策略。
