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TFEB 功能障碍介导 lysosomal 膜透诱导的 pyroptosis 在脱氧尼瓦诺暴露的肠表皮质中

Chun Zeng¹, Zhenyu Zou¹, Xinyi Cheng¹

¹Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang 330045, Jiangxi, P. R. China.

Journal of agricultural and food chemistry

|October 22, 2025

概括

脱氧尼瓦伦醇 (DON) 菌毒素通过破坏 lysosomes 和激活 pyroptosis 引起肠道细胞损伤. 恢复转录因子EB (TFEB) 功能可以防止DON引起的损伤,突出了TFEB.

科学领域:

毒理学毒理学毒理学
细胞生物学细胞生物学
胃肠病学胃肠病学

背景情况:

脱氧尼瓦伦醇 (DON) 是一种常见的谷物真菌毒素.
在肠道细胞中,DON会诱导溶酶体膜通透 (LMP).
LMP导致转录因子EB (TFEB) 功能障碍和热.

研究的目的:

调查TFEB在DON引起的肠损伤中的作用.
阐明链接 lysosomal 功能障碍与 pyroptosis 的机制.
探索TFEB作为DON毒性的治疗点.

主要方法:

在体内猪内和体内IPEC-J2细胞模型.
评估肠道屏障完整性,溶酶体标志物和热.
对TFEB活性和NLRP3炎症酶的药理学操纵.

主要成果:

暴露于DON引起了状缩,紧密结节的破坏和溶酶体泄漏.
DON 损害了TFEB核转位,激活了NLRP3炎症酶和热.
TFEB激活恢复了溶酶体完整性并减少了热;TFEB缺乏症使其恶化.
TFEB对LAMP1/LAMP2进行了上调,维持了溶酶体平衡.
抑制NLRP3并没有挽救TFEB缺陷细胞中的溶酶体完整性.

结论:

在DON毒性中,TFEB是连接 lysosomal 功能和 pyroptosis 的关键调节器.
TFEB功能障碍是DON诱导的肠上皮细胞烧灭的核心原因.
TFEB激活为DON诱导的肠损伤提供了潜在的治疗策略.

关键词:

在NLRP3炎症酶体中,NLRP3炎症脱氧尼瓦伦诺 (deoxynivalenolenol) 是一种除氧剂.溶酶体膜透性透化热致灭症是什么?转录因子EBEB是一个转录因子.

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