2. Academic Validation
  3. LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells

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

  • Virulence. 2023 Dec;14(1):2287339. doi: 10.1080/21505594.2023.2287339.
Weiting Mao 1,  Zhichao Wang 1,  Siting Wen 1 2,  Yan Lin 1 2,  Jiayun Gu 1 2,  Ju Sun 1 2,  Huan Wang 1 2,  Qi Cao 1 2,  Yindi Xu 3,  Xiaojuan Xu 1 2,  Xuwang Cai 1 2
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 2 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China.
  • 3 Institute of Animal Husbandry and Veterinary Research, Henan Academy of Agricultural Sciences, Zhengzhou, China.
PMID: 38018865 DOI: 10.1080/21505594.2023.2287339
Abstract

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.

Keywords

Glaesserella parasuis; LRRC8A; cell apoptosis; cytolethal distending toxin; p53 signalling.

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