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

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. 2023 May 20. doi: 10.1007/s11033-023-08403-7.
Xuan Zou 1 Chang Liu 1 Zuotian Huang 2 Song Xiang 2 Kaili Li 1 Yuan Yuan 1 Yingting Hao 1 Fachun Zhou 3
Affiliations

Affiliations

  • 1 Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
  • 2 Department of Hepatobiliary Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China.
  • 3 Department of Critical Care Medicine, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, PR China. zfc88@126.com.
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.

Keywords

ALI; Ferroptosis; HPMECs; STEAP1; sepsis.

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