Up‐regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
Up‐regulation of CHMP4B alleviates microglial necroptosis induced by traumatic brain injury
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CHMP4B上调可减轻创伤性脑损伤引起的小胶质细胞坏死性凋亡
DOI：
10.1111/jcmm.15406
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发表时间：
2020-06
影响因子：
5.3
通讯作者：
Pengzhan Zhao;Chong Li;Binglin Chen;Guangchi Sun;Honglu Chao;Yiming Tu;Zhongyuan Bao;Liang Fan-Liang-F
中科院分区：
文献类型：
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作者：
Pengzhan Zhao;Chong Li;Binglin Chen;Guangchi Sun;Honglu Chao;Yiming Tu;Zhongyuan Bao;Liang Fan-Liang-F
小胶质细胞是中枢神经系统的重要组成部分，在生理或病理条件下介导大脑的免疫反应。创伤性脑损伤（TBI）后，它往往会激活为促炎M1表型，并促进继发性脑损伤。最近，坏死性凋亡被发现促进TBI后小胶质细胞活化和神经炎症。然而，TBI后小胶质细胞坏死性凋亡的机制和具体干预措施仍缺乏研究。在这里，我们报道了过表达带电多泡体蛋白4 b（CHMP 4 B），这是转运复合物III（ESCRT-III）所需的内体分选的核心成员，可显著降低小胶质细胞的坏死性凋亡水平，改善神经功能恢复，并防止TBI后细胞死亡。进一步的研究表明，叉头转录因子O 1（FOXO 1）是一个关键的转录因子，通过结合到启动子区域增加CHMP 4 B的转录，从而抑制小胶质细胞的坏死性凋亡。以上结果表明，CHMP 4 B可减轻脑外伤后小胶质细胞坏死性凋亡和神经炎症反应，促进神经功能恢复。FOXO 1是促进CHMP 4 B表达的重要因子。本研究为脑外伤的预防和治疗提供了新的观点。
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.