Integrative Multi-Omics Analysis Identifies FTO as a Genetic and Epigenetic Link Between Metabolic Susceptibility and Staphylococcus aureus-Induced Airway Remodeling in Chronic Rhinosinusitis
Chem Biol Drug Des. 2026 Apr;107(4):e70297. doi: 10.1111/cbdd.70297.
ABSTRACT
This study identifies fat mass and obesity-associated protein (FTO) as a pivotal link between metabolic predisposition and pathogenesis associated with Staphylococcus aureus in chronic rhinosinusitis (CRS). These findings were established through the application of an integrative multi-omics framework. We demonstrate that S. aureus upregulates FTO, which functions as an m6A demethylase to stabilize the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). This molecular axis suppresses GSK-3Ξ² and promotes Ξ²-catenin nuclear translocation, thereby driving epithelial-mesenchymal transition (EMT) and pathological mucosal remodeling. By mapping the FTO-MALAT1-GSK-3Ξ²/Ξ²-catenin signaling network, this research elucidates how metabolic susceptibility facilitates infection-triggered epithelial reprogramming. These findings establish FTO as a promising biomarker and potential therapeutic target, providing a systemic foundation for personalized CRS treatment strategies.
PMID:41973807 | DOI:10.1111/cbdd.70297