Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery
Abstract CAAT/Enhancer Binding Protein β (C/EBPβ) is associated with inflammatory responses in neurodegenerative pathologies, particularly in the brain. However, the regulatory role of C/EBPβ in spinal cord injury and its impact on neurological recovery remain unknown. In this study, we observed sig...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Neuroinflammation |
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| Online Access: | https://doi.org/10.1186/s12974-025-03362-1 |
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| author | Jing Li Yubing Yang Chenguang Zhao Jinghao Zhao Xiaohui Wang Shengshou Ye Dong Wang Chengdong Zhou Jie Li Shuang Wang Ke Li Chunmiao Liu Xijing He Jie Qin |
| author_facet | Jing Li Yubing Yang Chenguang Zhao Jinghao Zhao Xiaohui Wang Shengshou Ye Dong Wang Chengdong Zhou Jie Li Shuang Wang Ke Li Chunmiao Liu Xijing He Jie Qin |
| author_sort | Jing Li |
| collection | DOAJ |
| description | Abstract CAAT/Enhancer Binding Protein β (C/EBPβ) is associated with inflammatory responses in neurodegenerative pathologies, particularly in the brain. However, the regulatory role of C/EBPβ in spinal cord injury and its impact on neurological recovery remain unknown. In this study, we observed significant upregulation of C/EBPβ in microglia after spinal cord injury in mice and was associated with neuroinflammation. Knocking down C/EBPβ in the spinal cord attenuated microglia pyroptosis, reduced the production of proinflammatory cytokines, and inhibited neuronal apoptosis. Mechanistically, C/EBPβ promoted the transcription of Fcgr1, which was involved in activating microglia pyroptosis. In both in-vivo and in-vitro experiments, knocking down Cebpb or Fcgr1, or the pyroptosis inhibitor VX765 inhibited neuronal apoptosis and improved neurological recovery in mice. These findings indicate that C/EBPβ functions as a key regulator that participates in the microglia pyroptosis-mediated neuroinflammation by activating Fcgr1 transcription. |
| format | Article |
| id | doaj-art-c4bb3a71f44f4b6d9a81d44e23e87691 |
| institution | Kabale University |
| issn | 1742-2094 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj-art-c4bb3a71f44f4b6d9a81d44e23e876912025-02-02T12:34:58ZengBMCJournal of Neuroinflammation1742-20942025-01-0122111810.1186/s12974-025-03362-1Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recoveryJing Li0Yubing Yang1Chenguang Zhao2Jinghao Zhao3Xiaohui Wang4Shengshou Ye5Dong Wang6Chengdong Zhou7Jie Li8Shuang Wang9Ke Li10Chunmiao Liu11Xijing He12Jie Qin13Department of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Rehabilitation Medicine, Xijing Hospital, Fourth Military Medical UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Spinal Surgery, Honghui Hospital, Xi’an Jiaotong UniversityDepartment of Neurology, Qinghai Cardiocerebrovascular Disease Specialised HospitalDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityInstitute of Photonics and Photon-technology, Northwest UniversityInstitute of Photonics and Photon-technology, Northwest UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Orthopedics, the Second Affiliated Hospital of Xi’an Jiaotong UniversityAbstract CAAT/Enhancer Binding Protein β (C/EBPβ) is associated with inflammatory responses in neurodegenerative pathologies, particularly in the brain. However, the regulatory role of C/EBPβ in spinal cord injury and its impact on neurological recovery remain unknown. In this study, we observed significant upregulation of C/EBPβ in microglia after spinal cord injury in mice and was associated with neuroinflammation. Knocking down C/EBPβ in the spinal cord attenuated microglia pyroptosis, reduced the production of proinflammatory cytokines, and inhibited neuronal apoptosis. Mechanistically, C/EBPβ promoted the transcription of Fcgr1, which was involved in activating microglia pyroptosis. In both in-vivo and in-vitro experiments, knocking down Cebpb or Fcgr1, or the pyroptosis inhibitor VX765 inhibited neuronal apoptosis and improved neurological recovery in mice. These findings indicate that C/EBPβ functions as a key regulator that participates in the microglia pyroptosis-mediated neuroinflammation by activating Fcgr1 transcription.https://doi.org/10.1186/s12974-025-03362-1C/EBPβSpinal cord injuryMicrogliaPyroptosisNeuroinflammation |
| spellingShingle | Jing Li Yubing Yang Chenguang Zhao Jinghao Zhao Xiaohui Wang Shengshou Ye Dong Wang Chengdong Zhou Jie Li Shuang Wang Ke Li Chunmiao Liu Xijing He Jie Qin Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery Journal of Neuroinflammation C/EBPβ Spinal cord injury Microglia Pyroptosis Neuroinflammation |
| title | Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| title_full | Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| title_fullStr | Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| title_full_unstemmed | Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| title_short | Microglial C/EBPβ-Fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| title_sort | microglial c ebpβ fcgr1 regulatory axis blocking inhibits microglial pyroptosis and improves neurological recovery |
| topic | C/EBPβ Spinal cord injury Microglia Pyroptosis Neuroinflammation |
| url | https://doi.org/10.1186/s12974-025-03362-1 |
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