2. Academic Validation
  3. Non-Canonical STING-PERK Pathway Modulation of Cellular Senescence and Therapeutic Response in Sepsis-Associated Acute Kidney Injury

Non-Canonical STING-PERK Pathway Modulation of Cellular Senescence and Therapeutic Response in Sepsis-Associated Acute Kidney Injury

  • Inflammation. 2024 Jun 24. doi: 10.1007/s10753-024-02081-8.
Yuxin Dong # 1,  Guanghe Liu # 1,  Xiaonan Situ # 1,  Lei Xia 1,  Tianyi Zhang 1,  Xiangxi Zhu 2,  Heng Jin 3,  Yancun Liu 4,  Songtao Shou 5
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
  • 2 Zunyi Medical University, No. 368 Jinwan Road, Jinhaian Community, Sanzao Town, Jinwan District, Zhuhai, 519041, Guangdong, China.
  • 3 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. hengjin@tmu.edu.cn.
  • 4 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. yancunliu@tmu.edu.cn.
  • 5 Department of Emergency Medicine, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. zyyshou@tmu.edu.cn.
  • # Contributed equally.
PMID: 38913144 DOI: 10.1007/s10753-024-02081-8
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.

Keywords

STING pathway; cell apoptosis; cellular senescence; inflammation; sepsis-associated acute kidney injury.

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