Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury
Summary: Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear....
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-05-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422400871X |
| _version_ | 1827284822066724864 |
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| author | Junjie Shen Liangzhi Gong Yi Sun Junqing Lin Wencheng Hu Jiabao Wei Xin Miao Tao Gao Jinlong Suo Jia Xu Yimin Chai Bingbo Bao Yun Qian Xianyou Zheng |
| author_facet | Junjie Shen Liangzhi Gong Yi Sun Junqing Lin Wencheng Hu Jiabao Wei Xin Miao Tao Gao Jinlong Suo Jia Xu Yimin Chai Bingbo Bao Yun Qian Xianyou Zheng |
| author_sort | Junjie Shen |
| collection | DOAJ |
| description | Summary: Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism. |
| first_indexed | 2024-04-24T10:03:47Z |
| format | Article |
| id | doaj.art-144874dd0b21438da37bf2f5563d539a |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T10:03:47Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-144874dd0b21438da37bf2f5563d539a2024-04-13T04:21:39ZengElsevieriScience2589-00422024-05-01275109649Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injuryJunjie Shen0Liangzhi Gong1Yi Sun2Junqing Lin3Wencheng Hu4Jiabao Wei5Xin Miao6Tao Gao7Jinlong Suo8Jia Xu9Yimin Chai10Bingbo Bao11Yun Qian12Xianyou Zheng13Department of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. ChinaDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. China; Corresponding authorDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. China; Corresponding authorDepartment of Orthopedic Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, P.R. China; Corresponding authorSummary: Excessive neuroinflammation after spinal cord injury (SCI) is a major hurdle during nerve repair. Although proinflammatory macrophage/microglia-mediated neuroinflammation plays important roles, the underlying mechanism that triggers neuroinflammation and aggravating factors remain unclear. The present study identified a proinflammatory role of semaphorin3C (SEMA3C) in immunoregulation after SCI. SEMA3C expression level peaked 7 days post-injury (dpi) and decreased by 14 dpi. In vivo and in vitro studies revealed that macrophages/microglia expressed SEMA3C in the local microenvironment, which induced neuroinflammation and conversion of proinflammatory macrophage/microglia. Mechanistic experiments revealed that RAGE/NF-κB was downstream target of SEMA3C. Inhibiting SEMA3C-mediated RAGE signaling considerably suppressed proinflammatory cytokine production, reversed polarization of macrophages/microglia shortly after SCI. In addition, inhibition of SEMA3C-mediated RAGE signaling suggested that the SEMA3C/RAGE axis is a feasible target to preserve axons from neuroinflammation. Taken together, our study provides the first experimental evidence of an immunoregulatory role for SEMA3C in SCI via an autocrine mechanism.http://www.sciencedirect.com/science/article/pii/S258900422400871XNatural sciencesBiological sciencesPhysiologyneurosciencesystems neurosciencesensory neuroscience |
| spellingShingle | Junjie Shen Liangzhi Gong Yi Sun Junqing Lin Wencheng Hu Jiabao Wei Xin Miao Tao Gao Jinlong Suo Jia Xu Yimin Chai Bingbo Bao Yun Qian Xianyou Zheng Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury iScience Natural sciences Biological sciences Physiology neuroscience systems neuroscience sensory neuroscience |
| title | Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| title_full | Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| title_fullStr | Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| title_full_unstemmed | Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| title_short | Semaphorin3C identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| title_sort | semaphorin3c identified as mediator of neuroinflammation and microglia polarization after spinal cord injury |
| topic | Natural sciences Biological sciences Physiology neuroscience systems neuroscience sensory neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S258900422400871X |
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