PANoptosis-like death in acute-on-chronic liver failure injury
Abstract The pathogenesis of Acute-on-chronic liver failure (ACLF) involves several forms of cell death, such as pyroptosis, apoptosis, and necroptosis, which consist of PANoptosis. To explore PANoptosis as a regulated cell death pathway in ACLF. Firstly, a bioinformatic strategy was used to observe...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-50720-1 |
| _version_ | 1797363476118634496 |
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| author | Qianling Ye Hanjing Wang Yue Chen Yihao Zheng Yuqiong Du Chongyang Ma Qiuyun Zhang |
| author_facet | Qianling Ye Hanjing Wang Yue Chen Yihao Zheng Yuqiong Du Chongyang Ma Qiuyun Zhang |
| author_sort | Qianling Ye |
| collection | DOAJ |
| description | Abstract The pathogenesis of Acute-on-chronic liver failure (ACLF) involves several forms of cell death, such as pyroptosis, apoptosis, and necroptosis, which consist of PANoptosis. To explore PANoptosis as a regulated cell death pathway in ACLF. Firstly, a bioinformatic strategy was used to observe the role of the PANoptosis pathway in ACLF and identify differentially expressed genes related to PANoptosis. Enrichment analysis showed that PANoptosis-related pathways were up-regulated in ACLF. We screened out BAX from the intersection of pyroptosis, apoptosis, necroptosis, and DEGs. Secondly, we screened articles from literature databases related to PANoptosis and liver failure, and specific forms of PANoptosis were reported in different experimental models in vitro and in vivo. Secondly, we established a model of ACLF using carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. A substantial release of inflammatory factors(IL-6, IL-18, TNFα, and IFNγ) and the key proteins of PANoptosis (NLRP3, CASP1, GSDMD, BAX, CASP8, CASP3, CASP7, and MLKL) were detected independently in the ACLF rats. Finally, we found that combining TNF-α/INF-γ inflammatory cytokines could induce L02 cells PANoptosis. Our study highlighted the potential role of ACLF and helps drug discovery targeting PANoptosis in the future. |
| first_indexed | 2024-03-08T16:20:56Z |
| format | Article |
| id | doaj.art-ebf4096bbbce4f26b29d0c4ac0c357e6 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-08T16:20:56Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ebf4096bbbce4f26b29d0c4ac0c357e62024-01-07T12:22:28ZengNature PortfolioScientific Reports2045-23222024-01-0114111910.1038/s41598-023-50720-1PANoptosis-like death in acute-on-chronic liver failure injuryQianling Ye0Hanjing Wang1Yue Chen2Yihao Zheng3Yuqiong Du4Chongyang Ma5Qiuyun Zhang6School of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversitySchool of Traditional Chinese Medicine, Capital Medical UniversityAbstract The pathogenesis of Acute-on-chronic liver failure (ACLF) involves several forms of cell death, such as pyroptosis, apoptosis, and necroptosis, which consist of PANoptosis. To explore PANoptosis as a regulated cell death pathway in ACLF. Firstly, a bioinformatic strategy was used to observe the role of the PANoptosis pathway in ACLF and identify differentially expressed genes related to PANoptosis. Enrichment analysis showed that PANoptosis-related pathways were up-regulated in ACLF. We screened out BAX from the intersection of pyroptosis, apoptosis, necroptosis, and DEGs. Secondly, we screened articles from literature databases related to PANoptosis and liver failure, and specific forms of PANoptosis were reported in different experimental models in vitro and in vivo. Secondly, we established a model of ACLF using carbon tetrachloride-induced liver fibrosis, followed by D-galactosamine and lipopolysaccharide joint acute attacks. A substantial release of inflammatory factors(IL-6, IL-18, TNFα, and IFNγ) and the key proteins of PANoptosis (NLRP3, CASP1, GSDMD, BAX, CASP8, CASP3, CASP7, and MLKL) were detected independently in the ACLF rats. Finally, we found that combining TNF-α/INF-γ inflammatory cytokines could induce L02 cells PANoptosis. Our study highlighted the potential role of ACLF and helps drug discovery targeting PANoptosis in the future.https://doi.org/10.1038/s41598-023-50720-1 |
| spellingShingle | Qianling Ye Hanjing Wang Yue Chen Yihao Zheng Yuqiong Du Chongyang Ma Qiuyun Zhang PANoptosis-like death in acute-on-chronic liver failure injury Scientific Reports |
| title | PANoptosis-like death in acute-on-chronic liver failure injury |
| title_full | PANoptosis-like death in acute-on-chronic liver failure injury |
| title_fullStr | PANoptosis-like death in acute-on-chronic liver failure injury |
| title_full_unstemmed | PANoptosis-like death in acute-on-chronic liver failure injury |
| title_short | PANoptosis-like death in acute-on-chronic liver failure injury |
| title_sort | panoptosis like death in acute on chronic liver failure injury |
| url | https://doi.org/10.1038/s41598-023-50720-1 |
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