Open AccessUp‐regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
Author(s) -
Zhao Pengzhan,
Li Chong,
Chen Binglin,
Sun Guangchi,
Chao Honglu,
Tu Yiming,
Bao Zhongyuan,
Fan Liang,
Du Xiaoliu,
Ji Jing
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15406
Subject(s) - necroptosis , neuroinflammation , microglia , traumatic brain injury , transcription factor , neuroscience , microbiology and biotechnology , inflammasome , programmed cell death , endosome , medicine , immunology , biology , inflammation , apoptosis , intracellular , biochemistry , psychiatry , gene
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.