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STAT3-Mediated Ferroptosis is Involved in Sepsis-Associated Acute Respiratory Distress Syndrome

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Abstract

Sepsis-induced acute respiratory distress syndrome (ARDS) poses a grave danger to life, resulting from sepsis-induced multi-organ failure. Although ferroptosis, a form of iron-dependent lipid peroxidative cell death, has been associated with sepsis-induced ARDS, the specific mechanisms are not fully understood. In this study, we utilized WGCNA, PPI, friends analysis, and six machine learning techniques (Lasso, SVM, RFB, XGBoost, AdaBoost, and LightGBM) to pinpoint STAT3 as a potential diagnostic marker. A significant increase in monocyte and neutrophil levels was observed in patients with sepsis-induced ARDS, as revealed by immune infiltration analyses, when compared to controls. Moreover, there was a positive correlation between STAT3 expression and the level of infiltration. Single-cell analysis uncovered a notable disparity in B-cell expression between sepsis and sepsis-induced ARDS. Furthermore, in vitro experiments using LPS-treated human bronchial epithelial cells (BEAS-2B) and THP1 cells demonstrated a significant increase in STAT3 phosphorylation expression. Additionally, the inhibition of STAT3 phosphorylation by Stattic effectively prevented LPS-induced ferroptosis in both BEAS-2B and THP1 cells. This indicates that the activation of STAT3 phosphorylation promotes ferroptosis in human bronchial epithelial cells in response to LPS. In summary, this research has discovered and confirmed STAT3 as a potential biomarker for the diagnosis and treatment of sepsis-induced ARDS.

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No datasets were generated or analyzed during the current study.

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Acknowledgements

We thank the Public Service Platform of South China Sea for R&D Marine Biomedicine Resources for support.

Funding

This research was funded by the Science and Technology Special Project of Zhanjiang (2022A01034) and the Science and Technology Program of Guangdong Province (2023A1515010850).

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  1. Shanshan Lin, Jiayu Yan and Wenjian Wang contributed equally.

Authors and Affiliations

  1. The Marine Biomedical Research Institute, The Marine Biomedical Research Institute of Guangdong Zhanjiang, School of Ocean and Tropical Medicine, Guangdong Medical University, Zhanjiang, Guangdong, 524023, China

    Shanshan Lin, Jiayu Yan, Wenjian Wang & Lianxiang Luo

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LXL conceived and designed the study. SSL and JYY analyzed data; WJW conducts experiments; SSL, WJW, LXL, and JYY wrote the manuscript; and LXL reviewed the paper and provided comments. All authors contributed to this manuscript and approved the submitted version.

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Correspondence to Lianxiang Luo.

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Lin, S., Yan, J., Wang, W. et al. STAT3-Mediated Ferroptosis is Involved in Sepsis-Associated Acute Respiratory Distress Syndrome. Inflammation (2024). https://doi.org/10.1007/s10753-024-01970-2

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