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<p>This study aimed to investigate the regulatory role of High-mobility group box 1 (HMGB1) in neuronal ferroptosis following spinal cord injury (SCI) and its underlying mechanisms. Iron ion deposition, malondialdehyde (MDA) and glutathione (GSH) levels, as well as the expressions of HMGB1, acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in spinal cord tissue of SCI rats were measured at 24&#xa0;h, 72&#xa0;h and 1 week post-injury. Then, an in vitro neuronal ferroptosis model was established and neuronal cells were transfected with lentiviral vectors for HMGB1 interference or ACSL4 overexpression. Iron ion levels, MDA content, GSH activity, and the expressions of HMGB1, ACSL4, SLC7A11 and GPX4 were measured. And the interaction between HMGB1 and ACSL4 was assessed. Finally, SCI rats were administered the HMGB1 inhibitor glycyrrhizic acid (GA) and the effects GA on the iron ion deposition, MDA and SOD levels, as well as the expressions of HMGB1, ACSL4, SLC7A11 and GPX4 in spinal cord tissues were evaluated. SCI induced time-dependent iron deposition, increased MDA, HMGB1, and ACSL4, and decreased GSH, GPX4, and SLC7A11. The administration of GA in SCI rats significantly reduces iron ion deposition, decreases the levels of MDA, HMGB1 and ACSL4, and increases the levels of GSH, GPX4, and SLC7A11. Furthermore, cellular-level results demonstrated that interfering with HMGB1 attenuated ferroptosis in rat spinal cord neurons by suppressing ACSL4. Targeted suppression of ACSL4 expression through interference with HMGB1 inhibits neuronal ferroptosis in SCI rats.</p>

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Interference with HMGB1 Inhibits Neuronal Ferroptosis Following Spinal Cord Injury through Targeting ACSL4

  • 期刊论文

  • 发表日期：

    2026年5月28日

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  • Zhiwu Wu,
  • Qinglin Zhong,
  • Tao Li,
  • Helan Yuan,
  • Tianxiang Zeng,
  • Jinshi Zhang,
  • Kaiming Feng,
  • Xinyun Ye,
  • Qiuhua Jiang,
  • Qianliang Huang

摘要

This study aimed to investigate the regulatory role of High-mobility group box 1 (HMGB1) in neuronal ferroptosis following spinal cord injury (SCI) and its underlying mechanisms. Iron ion deposition, malondialdehyde (MDA) and glutathione (GSH) levels, as well as the expressions of HMGB1, acyl-CoA synthetase long-chain family member 4 (ACSL4), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in spinal cord tissue of SCI rats were measured at 24 h, 72 h and 1 week post-injury. Then, an in vitro neuronal ferroptosis model was established and neuronal cells were transfected with lentiviral vectors for HMGB1 interference or ACSL4 overexpression. Iron ion levels, MDA content, GSH activity, and the expressions of HMGB1, ACSL4, SLC7A11 and GPX4 were measured. And the interaction between HMGB1 and ACSL4 was assessed. Finally, SCI rats were administered the HMGB1 inhibitor glycyrrhizic acid (GA) and the effects GA on the iron ion deposition, MDA and SOD levels, as well as the expressions of HMGB1, ACSL4, SLC7A11 and GPX4 in spinal cord tissues were evaluated. SCI induced time-dependent iron deposition, increased MDA, HMGB1, and ACSL4, and decreased GSH, GPX4, and SLC7A11. The administration of GA in SCI rats significantly reduces iron ion deposition, decreases the levels of MDA, HMGB1 and ACSL4, and increases the levels of GSH, GPX4, and SLC7A11. Furthermore, cellular-level results demonstrated that interfering with HMGB1 attenuated ferroptosis in rat spinal cord neurons by suppressing ACSL4. Targeted suppression of ACSL4 expression through interference with HMGB1 inhibits neuronal ferroptosis in SCI rats.