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Multi-omics reveals ferroptosis as a key mechanism in PM2.5-exacerbated periodontitis via gingival fibroblast damage
Yi He1, Lejia Zhang1, Shilin Jia1
1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510080, China.
Abstract:
PM2.5, a ubiquitous air pollutant, exacerbates periodontitis progression through mechanisms previously unclear. This study employed cytological and integrated transcriptomic-metabolomic analyses to investigate PM2.5's toxic effects on gingival fibroblasts. Results demonstrated that PM2.5 exposure decreased gingival fibroblasts viability, adhesion, and migration, while increased inflammation and disrupted mitochondrial homeostasis. Transcriptomics identified 7034 differentially expressed genes (DEGs) with 3834 upregulated and 3200 downregulated. KEGG enrichment revealed upregulated DEGs primarily associated with ferroptosis and ATP-dependent chromatin remodeling, while downregulated DEGs were enriched in extracellular matrix receptor interaction, focal adhesion, and PI3K-Akt signaling. Metabolomics identified 261 differentially expressed metabolites (DEMs) with 136 upregulated and 125 downregulated, which were involved in ferroptosis, glutathione metabolism, arginine biosynthesis, and glycerophospholipid metabolism. Mechanistically, PM2.5 induced ferroptosis in gingival fibroblasts via intracellular iron accumulation, lipid peroxidation, and imbalance of mitochondrial homeostasis, leading to cell death, which was suppressed by ferrostatin-1 (Fer-1). This study establishes a mechanistic link between environmental PM2.5 exposure and aggravated periodontitis, elucidating ferroptosis as a key contributor to gingival fibroblasts damage.
Insights
Fine particulate matter (PM2.5) worsens gum disease by causing cell death through ferroptosis in gingival fibroblasts. This research clarifies the cellular damage mechanism linking air pollution to periodontitis progression.
Area of Science:
- Environmental Health
- Cell Biology
- Genomics
Background:
- Particulate matter (PM2.5) is a major air pollutant linked to various health issues.
- The precise mechanisms by which PM2.5 affects periodontal tissues, specifically gingival fibroblasts, remain incompletely understood.
- Understanding these mechanisms is crucial for developing targeted interventions against pollution-exacerbated periodontitis.
Purpose of the Study:
- To investigate the toxic effects of PM2.5 on gingival fibroblasts.
- To elucidate the molecular mechanisms underlying PM2.5-induced damage in these cells.
- To establish a link between PM2.5 exposure and periodontitis progression.
Main Methods:
- Cytological assays to assess cell viability, adhesion, and migration.
- Integrated transcriptomic and metabolomic analyses to identify molecular changes.
- KEGG pathway enrichment analysis to understand biological processes involved.
- In vitro experiments using ferrostatin-1 (Fer-1) to test ferroptosis inhibition.
Main Results:
- PM2.5 exposure significantly reduced gingival fibroblast viability, adhesion, and migration.
- Transcriptomic data revealed alterations in genes related to ferroptosis and chromatin remodeling.
- Metabolomic data indicated dysregulation in pathways including ferroptosis, glutathione metabolism, and lipid metabolism.
- PM2.5 induced ferroptosis in gingival fibroblasts, characterized by iron accumulation and lipid peroxidation, which was preventable with Fer-1.
Conclusions:
- PM2.5 exposure induces significant cellular damage in gingival fibroblasts, contributing to periodontitis.
- Ferroptosis is identified as a key mechanism driving PM2.5-induced gingival fibroblast death.
- This study provides a mechanistic understanding of how air pollution (PM2.5) aggravates periodontitis.
