Timing, initiation and function: An in-depth exploration of the interaction network among neutrophil extracellular traps related genes in acute pancreatitis.

Autor: Zhang H; Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, PR China., Wang Z; Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, PR China., Li J; Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, PR China., Jia Y; Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, PR China., Li F; Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, PR China; Clinical Center for Acute Pancreatitis, Capital Medical University, Beijing, PR China. Electronic address: feili36@ccmu.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Nov 15; Vol. 141, pp. 112923. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1016/j.intimp.2024.112923
Abstrakt: Background: Exogenous inhibition of neutrophil extracellular traps (NETs) was believed to alleviate acute pancreatitis (AP). This study aimed to comprehensively explore the key biological behavior of NETs including timing and pathogenesis in AP by integrating of single cell RNA sequencing(scRNA-seq) and bulk RNA-seq.
Methods: Differentially expressed NETs-related genes and the hub genes of NETs were screened by bulk RNA-seq. ScRNA-seq was used to identify the cell types in pancreas of AP mice and to depict the transcriptomic maps in neutrophils. The mouse AP models were build to verify the timing of initiation of NETs and underlying pathogenesis of damage on pancreas acinar cells.
Results: Tlr4 and Ccl3 were screened for hub genes by bulk RNA-seq. The trajectory analysis of neutrophils showed that high expression of Ccl3, Cybb and Padi4 can be observed in the middle stage during AP. Macrophages might be essential in the biological behavior of neutrophils and NETs. Through animal models, we presented that extensive NETs structures were formed at mid-stage of inflammation, accompanied by more serious pancreas and lung damage. NETs might promote necroptosis and macrophage infiltration in AP, and the damage on pancreatic injury could be regulated by Tlr4 pathway. Ccl3 was considered to recruit neutrophils and promote NETs formation.
Conclusion: The findings explored the underlying timing and pathogenesis of NETs in AP for the first time, which provided gene targets for further studies.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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