Department of Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou, Henan, China.
Department of Intensive Care Unit, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
Mediators Inflamm. 2021 Jan 6;2021:5318369. doi: 10.1155/2021/5318369. eCollection 2021.
Acute kidney injury (AKI) is a common organ injury in sepsis, which leads to poor prognosis. Long noncoding RNA (lncRNA) small nucleolus RNA host gene 14 (SNHG14) was recognized to induce cell injury in LPS-induced acute lung injury and Parkinson's disease. We want to investigate the functions and mechanisms of SNHG14 in sepsis-induced AKI. Increased expression of SNHG14 was observed in LPS-induced HK-2 cells, and this was due to the activation of the TLR4/NF-B pathway. In vitro studies showed that SNHG14 was involved in the oxidative stress, inflammation, and apoptosis of LPS-induced HK-2 cells. Further investigations confirmed that SNHG14 exerted the functions via miR-93 which could regulate the activation of NF-B and STAT3 signaling by targeting IRAK4 and IL-6R. We also found that silencing SNHG14 also alleviated cellular injury processes of IL-1 and IL-6 in HK-2 cells via miR-93. We demonstrate that SNHG14 accelerates cellular injury in sepsis-induced AKI by activating IRAK4/NF-B and IL-6R/STAT3 signaling via miR-93.
急性肾损伤(AKI)是脓毒症中常见的器官损伤,导致预后不良。长链非编码 RNA(lncRNA)小核仁 RNA 宿主基因 14(SNHG14)被认为在 LPS 诱导的急性肺损伤和帕金森病中诱导细胞损伤。我们想研究 SNHG14 在脓毒症诱导的 AKI 中的作用和机制。在 LPS 诱导的 HK-2 细胞中观察到 SNHG14 的表达增加,这是由于 TLR4/NF-B 途径的激活。体外研究表明,SNHG14 参与 LPS 诱导的 HK-2 细胞的氧化应激、炎症和细胞凋亡。进一步的研究证实,SNHG14 通过 miR-93 发挥作用,通过靶向 IRAK4 和 IL-6R 来调节 NF-B 和 STAT3 信号的激活。我们还发现,沉默 SNHG14 还通过 miR-93 减轻 HK-2 细胞中 IL-1 和 IL-6 的细胞损伤过程。我们证明,SNHG14 通过 miR-93 激活 IRAK4/NF-B 和 IL-6R/STAT3 信号,加速脓毒症诱导的 AKI 中的细胞损伤。