中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (2): 730-741.doi: 10.4103/NRR.NRR-D-23-01854

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

FTO介导m6A修饰可调节创伤性脑损伤后的神经炎症反应

  

  • 出版日期:2026-02-15 发布日期:2025-05-24

Fat mass and obesity–mediated N6 -methyladenosine modification modulates neuroinflammatory responses after traumatic brain injury

Xiangrong Chen1, *, #, Jinqing Lai1, #, Zhe Wu1, #, Jianlong Chen1 , Baoya Yang1 , Chunnuan Chen2 , Chenyu Ding3, *   

  1. 1 Department of Neurosurgery, Second Clinical Medical College, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China;  2 Department of Neurology, Second Clinical Medical College, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China;  3 Department of Neurosurgery, Neurosurgery Research Institute, National Regional Medical Center, Binhai Campus, First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian Province, China
  • Online:2026-02-15 Published:2025-05-24
  • Contact: Xiangrong Chen, MD, xiangrong_chen281@126.com; Chenyu Ding, MD, dingcydr@163.com.
  • Supported by:
    This study was supported by grants from the Major Projects of Health Science Research Foundation for Middle-Aged and Young Scientist of Fujian Province, China, No. 2022ZQNZD01010010; the National Natural Science Foundation of China, No. 82371390; and Fujian Province Scientific Foundation, No. 2023J01725 (all to XC).

摘要:

活化小胶质细胞介导的神经炎症反应在创伤性脑损伤后继发性神经损伤中起着重要的作用。m6A转录后修饰在中枢神经系统免疫反应中普遍存在。FTO相关蛋白可调节前mRNA的剪接过程。然而,在创伤性脑损伤后,FTO在小胶质细胞激活以及随后的神经炎症反应中的作用仍不清楚。此次实验首先发现在脂多糖诱导的BV2细胞和创伤性脑损伤小鼠模型中FTO表达均显著下调。而抑制FTO表达后,随着BV2细胞中CD11b+/CD86+细胞比例以及促炎细胞因子分泌的增加,其呈现出促炎表型。FTO介导的m6A去甲基化加速了ADAM17 mRNA的降解,而FTO沉默则增强了ADAM17 mRNA的稳定性。因此,FTO表达下调可导致小胶质细胞中ADAM17的异常高表达,同时小胶质细胞的激活和由FTO相关的m6A修饰调节的神经炎症反应在创伤性脑损伤继发性损伤促炎过程中起着重要的作用。

https://orcid.org/0000-0001-9400-7358 (Xiangrong Chen); https://orcid.org/0000-0003-2358-1699 (Chenyu Ding)

Abstract: The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury. The posttranscriptional modification of N6 -methyladenosine is ubiquitous in the immune response of the central nervous system. The fat mass and obesity-related protein catalyzes the demethylation of N6 -methyladenosine modifications on mRNA and is widely expressed in various tissues, participating in the regulation of multiple diseases’ biological processes. However, the role of fat mass and obesity in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear. In this study, we found that the expression of fat mass and obesity was significantly down-regulated in both lipopolysaccharidetreated BV2 cells and a traumatic brain injury mouse model. After fat mass and obesity interference, BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b+ /CD86+ cells and the secretion of pro-inflammatory cytokines. Fat mass and obesity-mediated N6 -methyladenosine demethylation accelerated the degradation of ADAM17 mRNA, while silencing of fat mass and obesity enhanced the stability of ADAM17 mRNA. Therefore, down-regulation of fat mass and obesity expression leads to the abnormally high expression of ADAM17 in microglia. These results indicate that the activation of microglia and neuroinflammatory response regulated by fat mass and obesity-related N6 -methyladenosine modification plays an important role in the proinflammatory process of secondary injury following traumatic brain injury.

Key words: ADAM17, epigenetic modification, fat mass and obesity, N6 -methyladenosine, microglia, mRNA, nerve injury, neuroinflammation, traumatic brain injury, tumor necrosis factor α