LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells
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 cytol...
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| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2023.2287339 |
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| author | Weiting Mao Zhichao Wang Siting Wen Yan Lin Jiayun Gu Ju Sun Huan Wang Qi Cao Yindi Xu Xiaojuan Xu Xuwang Cai |
| author_facet | Weiting Mao Zhichao Wang Siting Wen Yan Lin Jiayun Gu Ju Sun Huan Wang Qi Cao Yindi Xu Xiaojuan Xu Xuwang Cai |
| author_sort | Weiting Mao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3e9986b8114a41a7b24206db3d092ed9 |
| institution | OA Journals |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-3e9986b8114a41a7b24206db3d092ed92025-08-20T02:38:22ZengTaylor & Francis GroupVirulence2150-55942150-56082023-12-0114110.1080/21505594.2023.2287339LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cellsWeiting Mao0Zhichao Wang1Siting Wen2Yan Lin3Jiayun Gu4Ju Sun5Huan Wang6Qi Cao7Yindi Xu8Xiaojuan Xu9Xuwang Cai10National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaInstitute of Animal Husbandry and Veterinary Research, Henan Academy of Agricultural Sciences, Zhengzhou, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaGlaesserella 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.https://www.tandfonline.com/doi/10.1080/21505594.2023.2287339Glaesserella parasuiscytolethal distending toxincell apoptosisp53 signallingLRRC8A |
| spellingShingle | Weiting Mao Zhichao Wang Siting Wen Yan Lin Jiayun Gu Ju Sun Huan Wang Qi Cao Yindi Xu Xiaojuan Xu Xuwang Cai LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells Virulence Glaesserella parasuis cytolethal distending toxin cell apoptosis p53 signalling LRRC8A |
| title | LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells |
| title_full | LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells |
| title_fullStr | LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells |
| title_full_unstemmed | LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells |
| title_short | LRRC8A promotes Glaesserella parasuis cytolethal distending toxin-induced p53-dependent apoptosis in NPTr cells |
| title_sort | lrrc8a promotes glaesserella parasuis cytolethal distending toxin induced p53 dependent apoptosis in nptr cells |
| topic | Glaesserella parasuis cytolethal distending toxin cell apoptosis p53 signalling LRRC8A |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2023.2287339 |
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