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Inhibition of Zbp1-PANoptosome-mediated PANoptosis effectively attenuates acute pancreatitis
Jie Li1,2, Yu-Chen Jia1,2, Jiongdi Lu1,2
1Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
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.
Insights
Early acute pancreatitis (AP) involves PANoptosis, a cell death pathway. Inhibiting Zbp1 significantly suppressed PANoptosis in AP models, offering a potential therapeutic strategy for this inflammatory disease.
Area of Science:
- Cellular Biology
- Immunology
- Gastroenterology
Background:
- Acute pancreatitis (AP) is an inflammatory condition characterized by multiple cell death modes.
- PANoptosis, encompassing pyroptosis, apoptosis, and necroptosis, is increasingly recognized in inflammatory diseases.
Purpose of the Study:
- To investigate the role of PANoptosis in acute pancreatitis.
- To identify key genes involved in PANoptosis during AP.
- To evaluate Zbp1 as a therapeutic target for AP.
Main Methods:
- Bioinformatic analysis of pancreatic transcriptome data.
- Identification of differentially expressed genes (DEGs) in AP.
- In vivo (mouse models) and in vitro (266-6 cell line) studies inhibiting Zbp1.
Main Results:
- PANoptosis pathways were enriched in AP.
- Zbp1 was identified as a key gene in PANoptosis.
- Inhibition of Zbp1 significantly suppressed PANoptosis in AP models.
Conclusions:
- Zbp1 plays a crucial role in Zbp1-PANoptosome-mediated PANoptosis in AP.
- Inhibiting Zbp1 can ameliorate inflammatory injury in AP.
- Targeting Zbp1 offers a promising therapeutic approach for acute pancreatitis.
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