2. Academic Validation
  3. Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury

Ferroptosis and inflammation are modulated by the NFIL3-ACSL4 axis in sepsis associated-acute kidney injury

  • Cell Death Discov. 2024 Aug 4;10(1):349. doi: 10.1038/s41420-024-02113-0.
Zhong Xiao 1 2 3,  Jie Zhang 4,  Zhimin Qiu 5,  Hongbing Liu 4,  Hua Ding 6,  Hi Li 1 2,  Yuanxin Liu 1 2,  Xiaohua Zou # 7 8,  Juan Long # 9 10
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
  • 2 College of Anesthesiology, Guizhou Medical University, Guiyang, China.
  • 3 Department of Critical Care Medicine, Shaoxing People's Hospital, Shaoxing, China.
  • 4 Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 Emergency Department, The First People's Hospital of Xiaoshan District, Hangzhou, China.
  • 6 Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
  • 7 Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China. zouxiaohuazxh@163.com.
  • 8 College of Anesthesiology, Guizhou Medical University, Guiyang, China. zouxiaohuazxh@163.com.
  • 9 Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China. doctorlong07@163.com.
  • 10 College of Anesthesiology, Guizhou Medical University, Guiyang, China. doctorlong07@163.com.
  • # Contributed equally.
PMID: 39097582 DOI: 10.1038/s41420-024-02113-0
Abstract

Sepsis-associated acute kidney injury (SA-AKI) increases the risk of death in patients with sepsis, and its major pathological change is the death of renal tubular cells. However, the mechanism of its occurrence remains unclear. Sepsis can lead to circadian dysregulation, and the rhythm gene NFIL3 has been reported to regulate lipid metabolism. There is compelling evidence that has demonstrated that lipid peroxidation can cause cellular Ferroptosis. In this study, we established the in vitro and in vivo models of SA-AKI and confirmed the presence of Ferroptosis of the renal tubular epithelial cells in SA-AKI. In addition, analysis of the GEO database showed that NFIL3 was highly expressed in sepsis patients and was highly correlated with the key molecule of Ferroptosis, ACSL4. The in vitro and in vivo data suggested that NFIL3 was involved in Ferroptosis and inflammation in SA-AKI. Subsequently, loss-of-function experiments revealed that NFIL3 knockdown attenuated Ferroptosis and inflammation in renal tubular epithelial cells by downregulating ACSL4 expression, thus protecting SA-AKI. In conclusion, this study is the first to illustrate the involvement of the rhythm gene NFIL3 in SA-AKI, providing new insights and potential therapeutic targets for SA-AKI.

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