School of Public Health, the key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 561113, China; Department of Epidemiology, College of Preventive Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Department of Epidemiology, College of Preventive Medicine, State Key Laboratory of Trauma and Chemical Poisoning, Army Medical University (Third Military Medical University), Chongqing 400038, China.
Toxicol Lett. 2024 Oct;400:81-92. doi: 10.1016/j.toxlet.2024.08.003. Epub 2024 Aug 13.
T-2 toxin is one of the mycotoxins widely distributed in human food and animal feed. Our recent work has shown that microglial activation may contribute to T-2 toxin-induced neurotoxicity. However, the molecular mechanisms involved need to be further clarified. To address this, we employed high-throughput transcriptome sequencing and found altered B cell translocation gene 2 (BTG2) expression levels in microglia following T-2 toxin treatment. It has been shown that altered BTG2 expression is involved in a range of neurological pathologies, but whether it's involved in the regulation of microglial activation is unclear. The aim of this study was to investigate the role of BTG2 in T-2 toxin-induced microglial activation. The results of animal experiments showed that T-2 toxin caused neurobehavioral disorders and promoted the expression of microglial BTG2 and pro-inflammatory activation of microglia in hippocampus and cortical, while microglial inhibitor minocycline inhibited these changes. The results of in vitro experiments showed that T-2 toxin enhanced BTG2 expression and pro-inflammatory microglial activation, and inhibited BTG2 expression weakened T-2 toxin-induced microglial activation. Moreover, T-2 toxin activated PI3K/AKT and its downstream NF-κB signaling pathway, which could be reversed after knock-down of BTG2 expression. Meanwhile, the PI3K inhibitor LY294002 also blocked this process. Therefore, BTG2 may be involved in T-2 toxin's ability to cause microglial activation through PI3K/AKT/NF-κB pathway.
T-2 毒素是广泛存在于人类食品和动物饲料中的一种真菌毒素。我们最近的工作表明，小胶质细胞激活可能导致 T-2 毒素诱导的神经毒性。然而，需要进一步阐明所涉及的分子机制。为了解决这个问题，我们采用了高通量转录组测序，发现 T-2 毒素处理后小胶质细胞中 B 细胞易位基因 2（BTG2）的表达水平发生改变。已经表明，BTG2 表达的改变涉及多种神经病理学，但它是否参与调节小胶质细胞激活尚不清楚。本研究旨在探讨 BTG2 在 T-2 毒素诱导的小胶质细胞激活中的作用。动物实验结果表明，T-2 毒素引起神经行为障碍，并促进海马和皮质中小胶质细胞 BTG2 的表达和促炎激活，而小胶质细胞抑制剂米诺环素抑制了这些变化。体外实验结果表明，T-2 毒素增强了 BTG2 的表达和促炎小胶质细胞的激活，而抑制 BTG2 的表达减弱了 T-2 毒素诱导的小胶质细胞激活。此外，T-2 毒素激活了 PI3K/AKT 及其下游 NF-κB 信号通路，BTG2 表达的敲低可逆转该过程。同时，PI3K 抑制剂 LY294002 也阻断了这一过程。因此，BTG2 可能通过 PI3K/AKT/NF-κB 通路参与 T-2 毒素引起小胶质细胞激活的能力。
