Abstract：
Abstract-This study explored the role of the non-canonical STING-PERK signaling pathway in sepsis-associated acute kidney injury (SA-AKI). Gene expression data from the GEO database and serum STING protein levels in patients with SA-AKI were analyzed. An LPS-induced mouse model and an in vitro model using HK-2 cells were used to investigate the role of STING in SA-AKI. STING expression was suppressed using shRNA silencing technology and the STING inhibitor C176. Kidney function, inflammatory markers, apoptosis, and senescence were measured. The role of the STING-PERK pathway was investigated by silencing PERK in HK-2 cells and administering the PERK inhibitor GSK2606414. STING mRNA expression and serum STING protein levels were significantly higher in patients with SA-AKI. Suppressing STING expression improved kidney function, reduced inflammation, and inhibited apoptosis and senescence. Silencing PERK or administering GSK2606414 suppressed the inflammatory response, cell apoptosis, and senescence, suggesting that PERK is a downstream effector in the STING signaling pathway. The STING-PERK signaling pathway exacerbates cell senescence and apoptosis in SA-AKI. Inhibiting this pathway could provide potential therapeutic targets for SA-AKI treatment.
摘要：
摘要-本研究探讨了非典型STING-PERK信号通路在脓毒症相关急性肾损伤（SA-AKI）中的作用。分析了来自GEO数据库的基因表达数据和SA-AKI患者的血清STING蛋白水平。使用LPS诱导的小鼠模型和使用HK-2细胞的体外模型来研究STING在SA-AKI中的作用。使用shRNA沉默技术和STING抑制剂C176抑制STING表达。肾功能,炎症标志物，凋亡，并测量衰老。通过沉默HK-2细胞中的PERK并施用PERK抑制剂GSK2606414来研究STING-PERK途径的作用。SA-AKI患者STINGmRNA表达和血清STING蛋白水平明显升高。抑制STING表达改善肾功能，减少炎症，并抑制细胞凋亡和衰老。沉默PERK或给予GSK2606414抑制炎症反应，细胞凋亡，和衰老，提示PERK是STING信号通路的下游效应子。STING-PERK信号通路加剧SA-AKI中的细胞衰老和凋亡。抑制该途径可以为SA-AKI治疗提供潜在的治疗靶标。
