H-151 attenuates lipopolysaccharide-induced acute kidney injury by inhibiting the STING–TBK1 pathway

Abstract

Sepsis is a severe systemic infectious disease that often leads to multi-organ dysfunction. One of the common and serious complications of sepsis is renal injury. In this study, we aimed to investigate the potential mechanistic role of a novel compound called H-151 in septic kidney injury. We also examined its impact on renal function and mouse survival rates. Initially, we confirmed abnormal activation of the STING–TBK1 signaling pathway in the kidneys of septic mice. Subsequently, we treated the mice with H-151 and observed significant improvement in sepsis-induced renal dysfunction. This was evidenced by reductions in blood creatinine and urea nitrogen levels, as well as a marked decrease in inflammatory cytokine levels. Furthermore, H-151 substantially improved the seven-day survival rate of septic mice, indicating its therapeutic potential. Importantly, H-151 also exhibited an inhibitory effect on renal apoptosis levels, further highlighting its mechanism of protecting against septic kidney injury. These study findings not only offer new insights into the treatment of septic renal injury but also provide crucial clues for further investigations into the regulatory mechanisms of the STING–TBK1 signaling pathway and potential drug targets.

Graphical Abstract

Keywords:

• STING–TBK1
• H-151
• sepsis
• acute kidney injury
• inflammation
• apoptosis

Acknowledgements

We appreciate the assistance provided by the FigDraw platform in terms of image resources.

Author contributions

Lei Xia, Yan-cun Liu, and Song-tao Shou designed the study. Lei Xia, Jie-yu Liu, and Jia-hui Jiang conducted the experiments. Yu-xin Dong, Qi-hui Liu and Tian-yi Zhang analyzed the data. Lei Xia, Jie-yu Liu wrote the manuscript. Yan-fen Chai and Song-tao Shou revised the paper and provided funding. All authors read and approved the final manuscript.

Ethical approval

All members included in this research, or their families, provided informed consent, and the Ethics Committee members at the General Hospital of Tianjin Medical University were sent a copy of the experimental procedures performed in this study for approval. The Animal Ethics Committee in the General Hospital of Tianjin Medical University granted its approval to all animal research experiments, based on the National Institute of Health (NIH) regulations (Ethical permit number: IRB2021-DW-52).

Consent form

All members included in this research, or their families, provided informed consent, and the Ethics Committee members at the General Hospital of Tianjin Medical University were sent a copy of the experimental procedures performed in this study for approval.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Any data involved in this study can be requested from the corresponding author.

Additional information

Funding

This work was funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-007A) and the Science and Technology Fund of Tianjin Municipal Health Bureau under Grant No. RK20001.