miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury
White matter injury (WMI) is the most frequent impairment of neurodevelopment in preterm infants. Here, we report that the caspase-1 inflammasome is abundantly activated in the microglia of WMI mice and results in increased pyroptosis of microglia. Pharmacology inhibition of caspase-1 cleavage allev...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2022/1642896 |
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| _version_ | 1832568848001269760 |
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| author | Liufang He Tingyan Wei Yong Huang Xueli Zhang Dongbo Zhu Huazhen Liu Zhangxing Wang |
| author_facet | Liufang He Tingyan Wei Yong Huang Xueli Zhang Dongbo Zhu Huazhen Liu Zhangxing Wang |
| author_sort | Liufang He |
| collection | DOAJ |
| description | White matter injury (WMI) is the most frequent impairment of neurodevelopment in preterm infants. Here, we report that the caspase-1 inflammasome is abundantly activated in the microglia of WMI mice and results in increased pyroptosis of microglia. Pharmacology inhibition of caspase-1 cleavage alleviated the pathogenesis of WMI mice. The expression of microRNA miR-214-3p was largely reduced in the microglia of WMI mice compared to controls. Compromised expression of miR-214-3p on microglia gives rise to the inflammasome activation and microglial pyroptosis. Treatment with miR-214-3p agomir is sufficient to relieve the white matter lesion and demyelination in WMI mice. miR-214-3p is able to bind to the 3′ region of the NLRP-3 inflammasome compartment NEK7, preventing the transcription of NEK7 mRNA. As a result, in WMI mice, the lack of miR-214-3p leads to the accumulation of NEK7 which supports NLRP 3 inflammasome activation, microglial pyroptosis, and white matter pathogenesis. |
| format | Article |
| id | doaj-art-6d938a6476354d4b9c3be8549a12f5cb |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-6d938a6476354d4b9c3be8549a12f5cb2025-02-03T00:12:17ZengWileyJournal of Immunology Research2314-71562022-01-01202210.1155/2022/1642896miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter InjuryLiufang He0Tingyan Wei1Yong Huang2Xueli Zhang3Dongbo Zhu4Huazhen Liu5Zhangxing Wang6Department of NeonatologyDepartment of NeonatologyDepartment of NeonatologyDepartment of NeonatologyDepartment of NeonatologySection of ImmunologyDepartment of NeonatologyWhite matter injury (WMI) is the most frequent impairment of neurodevelopment in preterm infants. Here, we report that the caspase-1 inflammasome is abundantly activated in the microglia of WMI mice and results in increased pyroptosis of microglia. Pharmacology inhibition of caspase-1 cleavage alleviated the pathogenesis of WMI mice. The expression of microRNA miR-214-3p was largely reduced in the microglia of WMI mice compared to controls. Compromised expression of miR-214-3p on microglia gives rise to the inflammasome activation and microglial pyroptosis. Treatment with miR-214-3p agomir is sufficient to relieve the white matter lesion and demyelination in WMI mice. miR-214-3p is able to bind to the 3′ region of the NLRP-3 inflammasome compartment NEK7, preventing the transcription of NEK7 mRNA. As a result, in WMI mice, the lack of miR-214-3p leads to the accumulation of NEK7 which supports NLRP 3 inflammasome activation, microglial pyroptosis, and white matter pathogenesis.http://dx.doi.org/10.1155/2022/1642896 |
| spellingShingle | Liufang He Tingyan Wei Yong Huang Xueli Zhang Dongbo Zhu Huazhen Liu Zhangxing Wang miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury Journal of Immunology Research |
| title | miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury |
| title_full | miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury |
| title_fullStr | miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury |
| title_full_unstemmed | miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury |
| title_short | miR-214-3p Deficiency Enhances Caspase-1-Dependent Pyroptosis of Microglia in White Matter Injury |
| title_sort | mir 214 3p deficiency enhances caspase 1 dependent pyroptosis of microglia in white matter injury |
| url | http://dx.doi.org/10.1155/2022/1642896 |
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