Identification of ferroptosis-related genes in periodontitis through bioinformatics analysis and experimental...

Periodontitis is a multifactorial chronic inflammatory disease of periodontal tissues. Ferroptosis is a form of regulated cell death, which is characterized by iron-dependent lipid peroxidation and involved in various inflammatory diseases. This study aims to identify ferroptosis-related genes associated with periodontitis and further validate their relevance through in vitro experiments.

Iron accumulation and localization were detected using Prussian blue staining. Differentially expressed genes in periodontitis were identified from GSE16134 and GSE10334, and intersected with ferroptosis genes to obtain differentially expressed ferroptosis genes (FerDEGs). Functional enrichment analyses of FerDEGs were performed by GO and KEGG. Hub genes were screened through PPI network analysis. The expression of these hub genes in gingival tissues and in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) with/without ferrostatin-1 (Fer-1) detected by qRT-PCR and Western Blot.

Ferroptosis was observed in gingival tissues affected by periodontitis. A total of 24 FerDEGs involved in periodontitis were identified. GO analysis and KEGG analysis highlighted the intrinsic apoptotic signaling pathway and ferroptosis as the top enriched pathways. PPI network analysis identified five hub genes. The mRNA expression levels of hub genes were significantly higher in inflammatory gingival tissues and HGFs stimulated with LPS (P < 0.05). The upregulated expression of PTGS2 and IL6 in HGFs were reversed by Fer-1 (P < 0.05).

This study highlights five ferroptosis-related genes as potential targets for future research into the pathogenesis of periodontitis.