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LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells

文献类型： 外文期刊

作者： Mao, Weiting 1 ; Wang, Zhichao 1 ; Wen, Siting 1 ; Lin, Yan 1 ; Gu, Jiayun 1 ; Sun, Ju 1 ; Wang, Huan 1 ; Cao, Qi 1 ; Xu, Yindi 3 ; Xu, Xiaojuan 1 ; Cai, Xuwang 1 ;

作者机构： 1.Huazhong Agr Univ, Coll Vet Med, Natl Key Lab Agr Microbiol, Wuhan, Peoples R China

2.Cooperat Innovat Ctr Sustainable Pig Prod, Key Lab Prevent Vet Med Hubei Prov, Wuhan, Peoples R China

3.Henan Acad Agr Sci, Inst Anim Husb & Vet Res, Zhengzhou, Peoples R China

关键词： Glaesserella parasuis; cytolethal distending toxin; cell apoptosis; p53 signalling; LRRC8A

期刊名称：VIRULENCE （ 影响因子：5.2； 五年影响因子：5.9 ）

ISSN： 2150-5594

年卷期： 2023 年 14 卷 1 期

页码：

收录情况： SCI

摘要： Glaesserella parasuis is an early colonizer of the swine upper respiratory tract and can break through the respiratory barrier for further invasion. However, the mechanisms underlying G. parasuis increases epithelial barrier permeability remain unclear. This study demonstrates that G. parasuis cytolethal distending toxin (CDT) induces p53-dependent apoptosis in new-born piglet tracheal (NPTr) cells. Moreover, we report for the first time that leucine-rich repeat-containing protein 8A (LRRC8A), an essential subunit of the volume-regulated anion channel (VRAC), involves in apoptosis of NPTr cells mediated by G. parasuis CDT. Pharmacological inhibition of VRAC with either PPQ-102 or NS3728 largely attenuated CDT-induced apoptosis in NPTr cells. Additionally, experiments with cells knocked down for LRRC8A using small interfering ribonucleic acid (siRNA) or knocked out LRRC8A using CRISPR/Cas9 technology showed a significant reduction in CDT-induced apoptosis. Conversely, re-expression of Sus scrofa LRRC8A in LRRC8A(-/-) NPTr cells efficiently complemented the CDT-induced apoptosis. In summary, these findings suggest that LRRC8A is pivotal for G. parasuis CDT-induced apoptosis, providing novel insights into the mechanism of apoptosis caused by CDT.

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