EPAS1 amplifies asthma pathogenesis through JAK2/STAT3-mediated ferroptosis and inflammation

Area of Science:

• Respiratory Medicine
• Molecular Biology
• Immunology

Background:

• Asthma involves airway inflammation and hyperresponsiveness, with underlying molecular mechanisms incompletely understood.
• Ferroptosis, a regulated cell death pathway, is implicated in asthma pathogenesis.

Purpose of the Study:

• To elucidate the role of the JAK2/STAT3/EPAS1 axis in regulating inflammation and ferroptosis in asthma.
• To identify potential diagnostic biomarkers and therapeutic targets for asthma.

Main Methods:

• Bioinformatic analysis of asthma datasets from the Gene Expression Omnibus (GEO) database.
• Weighted Gene Co-expression Network Analysis (WGCNA) and protein-protein interaction (PPI) network construction.
• Receiver Operating Characteristic (ROC) curve analysis and immune cell infiltration analysis.
• In vitro functional experiments assessing cell viability, inflammation, and ferroptosis.

Main Results:

• Identified 1,698 differentially expressed genes (DEGs) in asthma.
• Discovered five key hub genes (EPAS1, STAT3, G6PD, CYBB, CBS) with diagnostic value.
• Found EPAS1 is associated with immune cell infiltration in asthma.
• Demonstrated that the JAK2/STAT3 axis upregulates EPAS1, driving ferroptosis and inflammation.

Conclusions:

• The JAK2/STAT3/EPAS1 axis plays a critical role in asthma pathogenesis by promoting inflammation and ferroptosis.
• This axis represents a promising therapeutic target for asthma.
• Identified EPAS1, STAT3, G6PD, CYBB, and CBS as potential diagnostic biomarkers for asthma.