Sp1 Regulates the M1 Polarization of Microglia Through the HuR/NF-κB Axis after Spinal Cord Injury
Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved..
The M1 polarization of microglia, followed by the production of pro-inflammatory mediators, hinders functional recovery after spinal cord injury (SCI). Our previous study has illuminated that specificity protein 1 (Sp1) expression is increased following SCI, whereas the function and regulatory mechanism of Sp1 during M1 polarization of microglia following SCI remain unknown. RNA binding protein, HuR, has been shown to be up-regulated in the injured spinal cord through analysis of the GEO database. Further investigation using Chip-Atlas data suggests a binding between Sp1 and HuR. Emerging evidence indicates that HuR plays a pivotal role in neuroinflammation after SCI. In this research, Sp1 and HuR levels in mice with SCI and BV2 cells treated with lipopolysaccharide (LPS) was determined by using quantitative real-time polymerase chain reaction and Western blotting techniques. A series of in vitro assays were performed to investigate the function of Sp1 during M1 polarization of microglia. The association between Sp1 and its target gene HuR was confirmed through gene transfection and luciferase reporter assay. Enhanced expression of HuR was observed in both SCI mice and LPS-treated BV2 cells, while Sp1 knockdown restrained M1 polarization of microglia and its associated inflammation by inhibiting the NF-κB signaling pathway. Silencing Sp1 also suppressed microglia activation and its mediated inflammatory response, which could be reversed by overexpression of HuR. In conclusion, silencing Sp1 restrains M1 polarization of microglia through the HuR/NF-κB axis, leading to neuroprotection, and thus promotes functional restoration following SCI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:544 |
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| Enthalten in: |
Neuroscience - 544(2024) vom: 19. Apr., Seite 50-63 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Hangyu [VerfasserIn] |
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| Links: |
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| Themen: |
HuR |
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| Anmerkungen: |
Date Completed 08.04.2024 Date Revised 08.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neuroscience.2024.02.014 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a The M1 polarization of microglia, followed by the production of pro-inflammatory mediators, hinders functional recovery after spinal cord injury (SCI). Our previous study has illuminated that specificity protein 1 (Sp1) expression is increased following SCI, whereas the function and regulatory mechanism of Sp1 during M1 polarization of microglia following SCI remain unknown. RNA binding protein, HuR, has been shown to be up-regulated in the injured spinal cord through analysis of the GEO database. Further investigation using Chip-Atlas data suggests a binding between Sp1 and HuR. Emerging evidence indicates that HuR plays a pivotal role in neuroinflammation after SCI. In this research, Sp1 and HuR levels in mice with SCI and BV2 cells treated with lipopolysaccharide (LPS) was determined by using quantitative real-time polymerase chain reaction and Western blotting techniques. A series of in vitro assays were performed to investigate the function of Sp1 during M1 polarization of microglia. The association between Sp1 and its target gene HuR was confirmed through gene transfection and luciferase reporter assay. Enhanced expression of HuR was observed in both SCI mice and LPS-treated BV2 cells, while Sp1 knockdown restrained M1 polarization of microglia and its associated inflammation by inhibiting the NF-κB signaling pathway. Silencing Sp1 also suppressed microglia activation and its mediated inflammatory response, which could be reversed by overexpression of HuR. In conclusion, silencing Sp1 restrains M1 polarization of microglia through the HuR/NF-κB axis, leading to neuroprotection, and thus promotes functional restoration following SCI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a HuR | |
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| 650 | 4 | |a Spinal cord injury | |
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| 700 | 1 | |a Lin, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yufu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Helin |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jiyu |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wenbo |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Jinglong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Nanxiang |e verfasserin |4 aut | |
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