1. Up‐regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
- Author
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Binglin Chen, Jing Ji, Honglu Chao, Chong Li, Zhongyuan Bao, Pengzhan Zhao, Yiming Tu, Xiaoliu Du, Liang Fan, and Guangchi Sun
- Subjects
Adult ,Male ,0301 basic medicine ,Programmed cell death ,Traumatic brain injury ,Necroptosis ,microglia ,necroptosis ,FOXO1 ,Brain damage ,Cell Line ,Mice ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Brain Injuries, Traumatic ,Animals ,Humans ,Medicine ,CHMP4B ,Promoter Regions, Genetic ,Transcription factor ,Neuroinflammation ,Aged ,Inflammation ,Endosomal Sorting Complexes Required for Transport ,Microglia ,Forkhead Box Protein O1 ,business.industry ,traumatic brain injury ,Brain ,Original Articles ,Cell Biology ,Middle Aged ,medicine.disease ,Up-Regulation ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,Original Article ,medicine.symptom ,business ,Neuroscience - Abstract
Microglial cells are key component of central nervous system (CNS) and mediate the immune response of the brain under physiological or pathological conditions. It tends to activate into a pro‐inflammatory M1 phenotype after traumatic brain injury (TBI) and promote secondary brain damage. Recently, necroptosis was found to promote microglial activation and neuroinflammation after TBI. However, the mechanism and specific interventions of microglial necroptosis after TBI remain poorly investigated. Here, we reported that overexpress the charged multivesicular body protein 4b (CHMP4B) which is a core member of the endosomal sorting required for transport complex III (ESCRT‐III) significantly decreased the level of necroptosis in microglia, improved neurological function recovery and protected against cell death after TBI. Further investigation showed that forkhead transcription factor O1 (FOXO1) was a crucial transcription factor that increased CHMP4B transcription by binding to the promoter region, thereby inhibiting necroptosis in microglia. Collectively, our findings demonstrated that CHMP4B relieved microglial necroptosis and neuroinflammation after TBI, and promote the recovery of nerve function. FOXO1 is an important factor in promoting CHMP4B expression. This study provides the novel viewpoint for TBI prevention and treatment.
- Published
- 2020