LRRC8A在NPTr细胞中促进细胞致死性扩张毒素诱导的p53-依赖性亡
Weiting Mao1, Zhichao Wang1, Siting Wen1,2
1National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Virulence
|November 29, 2023
概括
Glaesserella parasuis细胞杀伤性扩张毒素 (CDT) 在小猪呼吸系统细胞中触发了编程细胞死亡. 这项研究确定了富含白的重复含有蛋白8A (LRRC8A) 对于这种CDT诱导的亡至关重要.
科学领域:
- 兽医微生物学 兽医微生物学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 格拉塞雷拉寄生虫 (Glaesserella parasuis) 殖民于猪的呼吸道,有可能突破表皮屏障.
- 通过G. parasuis增加上皮质透性的机制尚未完全理解.
研究的目的:
- 调查G.parasuis细胞致死性扩张毒素 (CDT) 在诱导小猪气管细胞的亡中的作用.
- 为了确定参与CDT介导的亡的分子参与者.
主要方法:
- 用G.parasuis CDT对新生猪的气管细胞 (NPTr) 的治疗.
- 使用PPQ-102和NS3728.2的体积调节离子通道 (VRAC) 的药理抑制.
- 使用siRNA对LRRC8A进行基因淘汰,使用CRISPR/Cas9.9进行基因淘汰.
- 在淘汰细胞中重新表达LRRC8A.
主要成果:
- 在NPTr细胞中,G.parasuis CDT诱导了p53-依赖的亡.
- 一个VRAC子单元,富含白的重复含有蛋白8A (LRRC8A) 被确定为CDT诱导的亡的关键.
- 抑制或耗尽LRRC8A显著降低了CDT诱导的亡,而重新表达恢复了它.
结论:
- LRRC8A在NPTr细胞中G.parasuis CDT诱导的亡中发挥着关键作用.
- 这些发现为CDT诱导的细胞死亡的分子机制提供了新的见解.
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