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Inhibition of STEAP1 ameliorates inflammation and ferroptosis of acute lung injury caused by sepsis in LPS-induced human pulmonary microvascular endothelial cells

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Abstract

Background

Ferroptosis plays an important part in Acute lung injury (ALI) caused by sepsis. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) has potential effects on iron metabolism and inflammation but reports on its function in ferroptosis and sepsis-caused ALI are lacking. Here we explored the role of STEAP1 in sepsis-caused ALI and the possible mechanisms.

Methods and results

Lipopolysaccharide (LPS) was added to human pulmonary microvascular endothelial cells (HPMECs) to form the sepsis-caused ALI model in vitro. The Cecal ligation and puncture (CLP) experiment was performed on C57/B6J mice to form the sepsis-caused ALI model in vivo. The effect of STEAP1 on inflammation was investigated by PCR, ELISA, and Western blot for the inflammatory factors and adhesion molecular. The reactive oxygen species (ROS) levels were detected by immunofluorescence. The effect of STEAP1 on ferroptosis was investigated by detecting malondialdehyde (MDA) levels, glutathione (GSH) levels, Fe2+ levels, cell viability, and mitochondrial morphology. Our findings suggested that STEAP1 expression was increased in the sepsis-induced ALI models. Inhibition of STEAP1 decreased the inflammatory response and ROS production as well as MDA levels but increased the levels of Nrf2 and GSH. Meanwhile, inhibition of STEAP1 improved cell viability and restored mitochondrial morphology. Western Blot results showed that inhibition of STEAP1 could affect the SLC7A11/GPX4 axis.

Conclusion

Inhibition of STEAP1 may be valuable for pulmonary endothelial protection in lung injury caused by sepsis.

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Data Availability

The data underlying this article will be shared on reasonable request to the corresponding author.

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Funding

This study was supported by Chongqing Municipal Health Commission (project number cstc2021ycjh-bgzxm0129) and Chongqing Municipal Education Commission (project number lpjd202001).

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Authors and Affiliations

  1. Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China

    Xuan Zou, Chang Liu, Kaili Li, Yuan Yuan, Yingting Hao & Fachun Zhou

  2. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China

    Zuotian Huang & Song Xiang

Authors
  1. Xuan Zou
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  2. Chang Liu
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  3. Zuotian Huang
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  4. Song Xiang
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  5. Kaili Li
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  6. Yuan Yuan
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  7. Yingting Hao
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  8. Fachun Zhou
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Contributions

F.Z. and X.Z. designed the research; X.Z. performed the experiments, analyzed the data, and wrote the manuscript; C.L., Z.H., S.X., K.L. analyzed the data; Y.Y. and Y.H. performed the experiments. F.Z. revised the manuscript. All authors approved the final manuscript.

Corresponding author

Correspondence to Fachun Zhou.

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There are no competing interests declared by the authors.

Ethical approval

The NIH Guide for the Care and Use of Laboratory Animals was adhered to in all animal research and the protocol was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (No.2021 − 704).

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Zou, X., Liu, C., Huang, Z. et al. Inhibition of STEAP1 ameliorates inflammation and ferroptosis of acute lung injury caused by sepsis in LPS-induced human pulmonary microvascular endothelial cells. Mol Biol Rep 50, 5667–5674 (2023). https://doi.org/10.1007/s11033-023-08403-7

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  • DOI: https://doi.org/10.1007/s11033-023-08403-7

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