FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway
Spinal cord injury (SCI) is a kind of traumatic nervous system disease caused by neuronal death, causing symptoms like sensory, motor, and autonomic nerve dysfunction. The recovery of neurological function has always been a intractable problem that has greatly distressed individuals and society. Alt...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923023001788 |
| _version_ | 1827810064399859712 |
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| author | Tianli Xu Qiancheng Zhu Qun Huang Qi Gu Yi Zhu Mengjie Tang Shoujin Tian Liming Wang Fei Yan Jianfei Ge Weiping Sha Xiaolong Lin |
| author_facet | Tianli Xu Qiancheng Zhu Qun Huang Qi Gu Yi Zhu Mengjie Tang Shoujin Tian Liming Wang Fei Yan Jianfei Ge Weiping Sha Xiaolong Lin |
| author_sort | Tianli Xu |
| collection | DOAJ |
| description | Spinal cord injury (SCI) is a kind of traumatic nervous system disease caused by neuronal death, causing symptoms like sensory, motor, and autonomic nerve dysfunction. The recovery of neurological function has always been a intractable problem that has greatly distressed individuals and society. Although the involvement of iron-dependent lipid peroxidation leading to nerve cell ferroptosis in SCI progression has been reported, the underlying mechanisms remain unaddressed. Thus, this study aimed to investigate the potential of recombinant human FGF21 (rhFGF21) in inhibiting ferroptosis of nerve cells and improving limb function after SCI, along with its underlying mechanisms. In vivo animal model showed that FGFR1, p-FGFR1, and β-Klotho protein gradually increased over time after injury, reaching a peak on the third day. Moreover, rhFGF21 treatment significantly reduced ACSL4, increased GPX4 expression, reduced iron deposition, and inhibited ferroptosis. Meanwhile, rhFGF21 decreased cell apoptosis following acute spinal cord damage. In contrast, FGFR1 inhibitor PD173074 partially reversed the rhFGF21-induced therapeutic effects. Overall, this work revealed that rhFGF21 activates the FGFR1/β-Klotho pathway to decrease ferroptosis of nerve cells, suggesting that FGF21 could be a new therapeutic target for SCI neurological rehabilitation. |
| first_indexed | 2024-03-11T22:48:27Z |
| format | Article |
| id | doaj.art-1f20e47d94ce439aaf26419aef645bcd |
| institution | Directory Open Access Journal |
| issn | 1873-2747 |
| language | English |
| last_indexed | 2024-03-11T22:48:27Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj.art-1f20e47d94ce439aaf26419aef645bcd2023-09-22T04:37:59ZengElsevierBrain Research Bulletin1873-27472023-10-01202110753FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathwayTianli Xu0Qiancheng Zhu1Qun Huang2Qi Gu3Yi Zhu4Mengjie Tang5Shoujin Tian6Liming Wang7Fei Yan8Jianfei Ge9Weiping Sha10Xiaolong Lin11Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaOrthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, China; Department of Endocrinology, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, ChinaDepartment of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, China; Corresponding authors at: Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China.Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China; Orthopaedics Laboratory, The First People’s Hospital of Zhangjiagang City, Suzhou 215600, China; Corresponding authors at: Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, China.Spinal cord injury (SCI) is a kind of traumatic nervous system disease caused by neuronal death, causing symptoms like sensory, motor, and autonomic nerve dysfunction. The recovery of neurological function has always been a intractable problem that has greatly distressed individuals and society. Although the involvement of iron-dependent lipid peroxidation leading to nerve cell ferroptosis in SCI progression has been reported, the underlying mechanisms remain unaddressed. Thus, this study aimed to investigate the potential of recombinant human FGF21 (rhFGF21) in inhibiting ferroptosis of nerve cells and improving limb function after SCI, along with its underlying mechanisms. In vivo animal model showed that FGFR1, p-FGFR1, and β-Klotho protein gradually increased over time after injury, reaching a peak on the third day. Moreover, rhFGF21 treatment significantly reduced ACSL4, increased GPX4 expression, reduced iron deposition, and inhibited ferroptosis. Meanwhile, rhFGF21 decreased cell apoptosis following acute spinal cord damage. In contrast, FGFR1 inhibitor PD173074 partially reversed the rhFGF21-induced therapeutic effects. Overall, this work revealed that rhFGF21 activates the FGFR1/β-Klotho pathway to decrease ferroptosis of nerve cells, suggesting that FGF21 could be a new therapeutic target for SCI neurological rehabilitation.http://www.sciencedirect.com/science/article/pii/S0361923023001788Spinal cord injuryFerroptosisRhFGF21FGFR1P-FGFR1β-Klotho |
| spellingShingle | Tianli Xu Qiancheng Zhu Qun Huang Qi Gu Yi Zhu Mengjie Tang Shoujin Tian Liming Wang Fei Yan Jianfei Ge Weiping Sha Xiaolong Lin FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway Brain Research Bulletin Spinal cord injury Ferroptosis RhFGF21 FGFR1 P-FGFR1 β-Klotho |
| title | FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway |
| title_full | FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway |
| title_fullStr | FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway |
| title_full_unstemmed | FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway |
| title_short | FGF21 prevents neuronal cell ferroptosis after spinal cord injury by activating the FGFR1/β-Klotho pathway |
| title_sort | fgf21 prevents neuronal cell ferroptosis after spinal cord injury by activating the fgfr1 β klotho pathway |
| topic | Spinal cord injury Ferroptosis RhFGF21 FGFR1 P-FGFR1 β-Klotho |
| url | http://www.sciencedirect.com/science/article/pii/S0361923023001788 |
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