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Roles of PANoptosis and related genes in acute liver failure: neoteric insight from bioinformatics analysis and animal experiment verification

  • 0State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Journal of Zhejiang University. Science. B +

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April 24, 2025

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April 24, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

PANoptosis, a cell death form, drives acute liver failure (ALF) development. Seven identified biomarkers may offer new diagnostic and therapeutic targets for ALF.

Area Of Science

  • Cellular and Molecular Biology
  • Immunology
  • Hepatology

Background

  • PANoptosis integrates pyroptosis, apoptosis, and necroptosis, with roles in acute liver failure (ALF) understudied.
  • Crosstalk among cell death pathways in ALF pathogenesis requires further investigation.

Purpose Of The Study

  • To investigate the role of PANoptosis in ALF.
  • To identify novel molecular targets for ALF prevention and treatment.

Main Methods

  • Utilized Gene Expression Omnibus (GEO) datasets (GSE14668, GSE62029, GSE74000) to identify differentially expressed genes (DEGs) in ALF.
  • Integrated DEGs, Weighted Gene Co-expression Network Analysis (WGCNA), and PANoptosis-related genes to identify hub genes.
  • Performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and gene set enrichment analysis (GSEA) for functional determination, validated in an ALF mouse model.

Main Results

  • Identified seven hub genes (BMF, BNIP3L, CASP1, RIPK3, UACA, UNC5B, ZBP1) with altered expression in ALF patients and models.
  • Observed differential expression patterns of these genes and their related pathways (pyroptosis, apoptosis, necroptosis) in ALF progression.
  • Confirmed macrophage involvement in PANoptosis and PANoptosome formation in ALF, particularly in response to LPS stimulation.

Conclusions

  • PANoptosis, particularly in macrophages, significantly contributes to ALF development.
  • The seven validated hub genes represent potential diagnostic biomarkers and therapeutic targets for ALF.

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