DNAJB9 promotes epithelial-mesenchymal transition in the nasal epithelium of chronic rhinosinusitis by enhancing TRIM22-mediated IκBα degradation.

This study investigates the functional role of DNAJB9 in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Using quantitative proteomics alongside human tissue analysis and murine models, we found that DNAJB9 is significantly upregulated in CRSwNP nasal epithelium and closely mirrors epithelial-mesenchymal transition (EMT) progression. Functional assays in human epithelial cells demonstrated that DNAJB9 actively drives the EMT phenotype. Mechanistically, DNAJB9 interacts with and stabilizes the E3 ubiquitin ligase TRIM22 by inhibiting its autoubiquitination. This stabilized TRIM22 targets IκBα for proteasomal degradation, leading to constitutive NF-κB pathway activation and subsequent EMT. Ultimately, DNAJB9 acts as an essential driver of tissue remodeling in CRSwNP. These findings highlight the broader clinical significance of the DNAJB9/TRIM22/NF-κB signaling axis, presenting it as a promising therapeutic target for inhibiting nasal polyp formation and associated remodeling.