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<p>Trichloroethylene (TCE) is widely employed as a cleaning agent in industrial settings. Occupational exposure to TCE can lead to occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Our previous research has identified damage to renal vascular endothelial cells (ECs) in both OMDT patients and TCE-sensitized mice; however, the underlying mechanisms remain insufficiently understood. Methods: This study aims to elucidate the role of endoplasmic reticulum stress (ERS)-induced ECs ferroptosis in TCE-induced renal injury by developing a TCE-sensitization mouse model. Our findings indicate that ferroptosis in renal ECs is associated with TCE-induced kidney damage, and the ferroptosis inhibitor Fer-1 can mitigate this injury. Notably, ERS can modulate TCE-induced ECs ferroptosis. The PERK inhibitor GSK2606414 can suppress ferroptosis via the Nrf2/HO-1 signaling pathway and reduce trichloroethylene-induced renal injury. In conclusion, TCE sensitization activates ERS through the PERK/eIF2α/ATF4 pathway, with PERK subsequently mediating ferroptosis of renal vascular endothelial cells via the Nrf2/HO-1 signaling pathway, thereby contributing to TCE-related immune kidney injury.</p> Graphical abstract <p></p>

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Mechanism of endoplasmic reticulum stress-induced endothelial cell ferroptosis in trichloroethylene-induced mouse kidney injury

  • 期刊论文

  • 发表日期：

    2025年7月26日

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  • Meng Huang,
  • Jiaxiang Zhang,
  • Rui Li,
  • Jian Chen,
  • Qixing Zhu,
  • Haibo Xie

摘要

Trichloroethylene (TCE) is widely employed as a cleaning agent in industrial settings. Occupational exposure to TCE can lead to occupational medicamentose-like dermatitis due to trichloroethylene (OMDT). Our previous research has identified damage to renal vascular endothelial cells (ECs) in both OMDT patients and TCE-sensitized mice; however, the underlying mechanisms remain insufficiently understood. Methods: This study aims to elucidate the role of endoplasmic reticulum stress (ERS)-induced ECs ferroptosis in TCE-induced renal injury by developing a TCE-sensitization mouse model. Our findings indicate that ferroptosis in renal ECs is associated with TCE-induced kidney damage, and the ferroptosis inhibitor Fer-1 can mitigate this injury. Notably, ERS can modulate TCE-induced ECs ferroptosis. The PERK inhibitor GSK2606414 can suppress ferroptosis via the Nrf2/HO-1 signaling pathway and reduce trichloroethylene-induced renal injury. In conclusion, TCE sensitization activates ERS through the PERK/eIF2α/ATF4 pathway, with PERK subsequently mediating ferroptosis of renal vascular endothelial cells via the Nrf2/HO-1 signaling pathway, thereby contributing to TCE-related immune kidney injury.

Graphical abstract