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.