Department of Emergency, First Hospital of Quanzhou affiliated to Fujian Medical University, Fujian, Quanzhou, China.
J Int Med Res. 2021 Aug;49(8):3000605211037495. doi: 10.1177/03000605211037495.
This study aimed to clarify the mechanism by which the long non-coding RNA cancer susceptibility candidate 9 (CASC9) alleviates sepsis-related acute kidney injury (S-AKI).
A lipopolysaccharide (LPS)-induced AKI model was established to simulate S-AKI. HK-2 human renal tubular epithelial cells were treated with LPS to establish an model, and mice were intraperitoneally injected with LPS to generate an model. Subsequently, the mRNA expression of inflammatory and antioxidant factors was validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Reactive oxygen species (ROS) production was assessed using an assay kit. Apoptosis was detected by western blotting and fluorescence-activated cell sorting.
CASC9 was significantly downregulated in the LPS-induced AKI model. CASC9 attenuated cell inflammation and apoptosis and enhanced the antioxidant capacity of cells. Regarding the mechanism, miR-424-5p was identified as the downstream target of CASC9, and the interaction between CASC9 and miR-424-5p promoted thioredoxin-interacting protein (TXNIP) expression.
CASC9 alleviates LPS-induced AKI and in , and CASC9 directly targets miR-424-5p and further promotes the expression of TXNIP. We have provided a possible reference strategy for the treatment of S-AKI.
本研究旨在阐明长链非编码 RNA 癌症易感性候选物 9（CASC9）缓解脓毒症相关急性肾损伤（S-AKI）的机制。
建立脂多糖（LPS）诱导的 AKI 模型模拟 S-AKI。用 LPS 处理人肾小管上皮细胞（HK-2）建立 模型，并用 LPS 腹腔注射小鼠生成 模型。然后，通过定量逆转录聚合酶链反应（RT-qPCR）验证炎症和抗氧化因子的 mRNA 表达。使用试剂盒评估活性氧（ROS）的产生。通过蛋白质印迹和流式细胞术检测细胞凋亡。
在 LPS 诱导的 AKI 模型中，CASC9 的表达显著下调。CASC9 可减轻细胞炎症和凋亡，并增强细胞的抗氧化能力。关于其机制，miR-424-5p 被鉴定为 CASC9 的下游靶标，CASC9 与 miR-424-5p 的相互作用促进了硫氧还蛋白相互作用蛋白（TXNIP）的表达。
CASC9 缓解 LPS 诱导的 AKI ，并在 中，CASC9 直接靶向 miR-424-5p，进一步促进 TXNIP 的表达。我们为 S-AKI 的治疗提供了一种可能的参考策略。
