Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis

Abstract Early acute pancreatitis is an acute inflammatory disease that involves multiple modes of cell death, including apoptosis, necrotic apoptosis, and pyroptosis in its disease process. PANoptosis, a type of cell death that includes pyroptosis, apoptosis, and necroptosis, has had an important r...

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Main Authors: Jie Li, Yu-chen Jia, Jiongdi Lu, Haoyu Zhang, Zheng Wang, Xiaozhou Xie, Feng Cao, Fei Li
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-025-02451-7
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author Jie Li
Yu-chen Jia
Jiongdi Lu
Haoyu Zhang
Zheng Wang
Xiaozhou Xie
Feng Cao
Fei Li
author_facet Jie Li
Yu-chen Jia
Jiongdi Lu
Haoyu Zhang
Zheng Wang
Xiaozhou Xie
Feng Cao
Fei Li
author_sort Jie Li
collection DOAJ
description Abstract Early acute pancreatitis is an acute inflammatory disease that involves multiple modes of cell death, including apoptosis, necrotic apoptosis, and pyroptosis in its disease process. PANoptosis, a type of cell death that includes pyroptosis, apoptosis, and necroptosis, has had an important role in a variety of infectious and inflammatory diseases in recent years. To judge the relationship between PANoptosis and AP, we first analyzed the data from pancreatic transcriptome data by bioinformatics techniques, and we found the enrichment of PANoptosis pathway in AP. Next, we screened the genes and identified differentially expressed genes (DEGs) associated with AP and PANoptosis. Finally, we found that Zbp1 may have a major role in the process of PANoptosis. For this purpose, we constructed AP models in mice and in vitro cell line 266-6 and intervened by inhibiting Zbp1. The final results showed that the PANoptosis in mice was significantly suppressed after inhibition of Zbp1. In conclusion, inflammatory injury in AP can be significantly improved by inhibiting Zbp1- PANoptosome-mediated PANoptosis.
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issn 2058-7716
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publishDate 2025-04-01
publisher Nature Publishing Group
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series Cell Death Discovery
spelling doaj-art-ecf07a75971a44cd9dff0d617785382b2025-08-20T02:17:49ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111110.1038/s41420-025-02451-7Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitisJie Li0Yu-chen Jia1Jiongdi Lu2Haoyu Zhang3Zheng Wang4Xiaozhou Xie5Feng Cao6Fei Li7Department of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityDepartment of General Surgery, Xuanwu Hospital, Capital Medical UniversityAbstract Early acute pancreatitis is an acute inflammatory disease that involves multiple modes of cell death, including apoptosis, necrotic apoptosis, and pyroptosis in its disease process. PANoptosis, a type of cell death that includes pyroptosis, apoptosis, and necroptosis, has had an important role in a variety of infectious and inflammatory diseases in recent years. To judge the relationship between PANoptosis and AP, we first analyzed the data from pancreatic transcriptome data by bioinformatics techniques, and we found the enrichment of PANoptosis pathway in AP. Next, we screened the genes and identified differentially expressed genes (DEGs) associated with AP and PANoptosis. Finally, we found that Zbp1 may have a major role in the process of PANoptosis. For this purpose, we constructed AP models in mice and in vitro cell line 266-6 and intervened by inhibiting Zbp1. The final results showed that the PANoptosis in mice was significantly suppressed after inhibition of Zbp1. In conclusion, inflammatory injury in AP can be significantly improved by inhibiting Zbp1- PANoptosome-mediated PANoptosis.https://doi.org/10.1038/s41420-025-02451-7
spellingShingle Jie Li
Yu-chen Jia
Jiongdi Lu
Haoyu Zhang
Zheng Wang
Xiaozhou Xie
Feng Cao
Fei Li
Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
Cell Death Discovery
title Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
title_full Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
title_fullStr Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
title_full_unstemmed Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
title_short Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
title_sort inhibition of zbp1 panoptosome mediated panoptosis effectively attenuates acute pancreatitis
url https://doi.org/10.1038/s41420-025-02451-7
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