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Exploring the interconnection between PANoptosis and chronic inflammatory diseases: identifying key targets and therapeutic strategies for periodontitis and ulcerative colitis

  • 0Department of Stomatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, China.
Naunyn-Schmiedeberg's Archives of Pharmacology +

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July 2, 2025

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July 2, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study reveals PANoptosis as a key link between periodontitis (PD) and ulcerative colitis (UC), identifying BAG3, LYN, and APOE as potential therapeutic targets for these chronic inflammatory diseases.

Area Of Science

  • Immunology
  • Genetics
  • Molecular Biology

Background

  • Periodontitis (PD) and ulcerative colitis (UC) are chronic inflammatory diseases with shared molecular pathways.
  • PANoptosis, a cell death process integrating pyroptosis, apoptosis, and necroptosis, may mediate these shared mechanisms.
  • Identifying shared targets could lead to novel therapeutic strategies for co-occurring oral and intestinal inflammation.

Purpose Of The Study

  • To identify key genes and pathways linking PD and UC.
  • To explore the interaction between PANoptosis-related genes and PD-UC-associated genes.
  • To predict potential therapeutic targets and drugs for PD and UC.

Main Methods

  • Utilized GEO datasets (GSE16134 for PD, GSE87466 for UC) for differential expression and WGCNA analysis.
  • Integrated PD-UC and PANoptosis gene sets, constructing protein-protein interaction networks and performing enrichment analyses (GO, KEGG).
  • Identified core genes using LASSO and SVM-RFE, validated in mouse models and single-cell RNA sequencing, and predicted therapeutic drugs via ceRNA network and molecular docking.

Main Results

  • Identified 107 intersected genes, with BAG3, LYN, and APOE as core targets significantly linked to immune and inflammatory pathways.
  • Validated differential expression of core genes in PD and DSS-induced UC mouse models.
  • Single-cell RNA sequencing showed cell-type-specific expression (Lyn in myeloid cells, Apoe in fibroblasts), and drug prediction identified potential agents for LYN and APOE.

Conclusions

  • BAG3, LYN, and APOE are identified as key molecular targets bridging PANoptosis with periodontitis and ulcerative colitis.
  • PANoptosis represents a novel therapeutic axis for managing chronic inflammatory comorbidities affecting oral and intestinal mucosa.
  • This research provides a foundation for developing targeted therapies for linked inflammatory conditions.

Keywords:

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