Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (7): 1568-1574.doi: 10.4103/1673-5374.387979

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Fibroblast growth factor 21 inhibits ferroptosis following spinal cord injury by regulating heme oxygenase-1

Qi Gu1, 2, #, Weiping Sha1, 2, #, Qun Huang1, 2, Jin Wang1, 2, Yi Zhu1, 2, Tianli Xu1, 2, Zhenhua Xu3, Qiancheng Zhu1, 2, Jianfei Ge1, 2,  Shoujin Tian1, 2, *, Xiaolong Lin1, 2, *   

  1. 1Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China; 2Orthopedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou, Jiangsu Province, China; 3Department of Anesthesiology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China
  • Online:2024-07-15 Published:2023-11-28
  • Contact: Shoujin Tian, BS, tiansurgeon@163.com; Xiaolong Lin, PhD, drlinxiaolong@163.com.
  • Supported by:
    This work was supported by grants from Jiangsu Commission of Health, No. Z2021086 (to XL); Science and Technology Program of Suzhou, Nos. SYSD2020008 (to XL), SKYD2022012 (to XL); Suzhou Municipal Health Commission, No. KJXW2020058 (to XL); and Science and Technology Program of Zhangjiagang, No. ZKS2018 (to XL).

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Abstract: Interfering with the ferroptosis pathway is a new strategy for the treatment of spinal cord injury. Fibroblast growth factor 21 can inhibit ferroptosis and promote neurofunctional recovery, while heme oxygenase-1 is a regulator of iron and reactive oxygen species homeostasis. The relationship between heme oxygenase-1 and ferroptosis remains controversial. In this study, we used a spinal cord injury rat model to show that the levels of fibroblast growth factor 21 in spinal cord tissue decreased after spinal cord injury. In addition, there was a significant aggravation of ferroptosis and a rapid increase in heme oxygenase-1 expression after spinal cord injury. Further, heme oxygenase-1 aggravated ferroptosis after spinal cord injury, while fibroblast growth factor 21 inhibited ferroptosis by downregulating heme oxygenase-1. Thus, the activation of fibroblast growth factor 21 may provide a potential treatment for spinal cord injury. These findings could provide a new potential mechanistic explanation for fibroblast growth factor 21 in the treatment of spinal cord injury.

Key words: ferroptosis, fibroblast growth factor 21, functional recovery, heme oxygenase-1, lipid peroxidation, neuron, reactive oxygen species, spinal cord injury