International dental journal · 2026
Fusobacterium nucleatum-Derived Outer Membrane Vesicles Disrupt Epithelial Barrier in Oral Lichen Planus via JNK/c-JUN Mediated Claudin-4 Downregulation.
СтатьяНазвание и аннотация: Перевод в очереди
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Shao Ruru, Wang Zhenyuan, Yang Chenglong, Chen Junjun, Du Guanhuan
Аннотация
INTRODUCTION AND AIMS: Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. Recent studies have implicated microbial dysbiosis in its pathogenesis. Our previous research revealed an increased abundance of Fusobacterium nucleatum (F.nucleatum) in OLP tissues, suggesting its potential involvement.
METHODS: We utilized single-cell RNA sequencing, spatial transcriptomics, and immunohistochemistry to analyse Claudin-4 expression and its spatial distribution in OLP lesions. In vitro, HaCaT keratinocytes exposed to outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) were evaluated for epithelial barrier function via transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD4) permeability assays. Claudin-4 expression and JNK/c-JUN pathway activation were evaluated by qPCR, Western blotting, and RNA sequencing. The JNK inhibitor SP600125 was used to explore pathway involvement.
RESULTS: Claudin-4 expression was significantly decreased and exhibited disrupted spatial organization in OLP lesions. F.n-OMVs compromised HaCaT epithelial barrier function, downregulated Claudin-4 expression, and altered its localization. Western blotting demonstrated activation of the JNK/c-JUN signaling pathway. Inhibition of JNK with SP600125 restored Claudin-4 expression and barrier function.
CONCLUSION: Our study demonstrates that F.n-OMVs induce epithelial barrier dysfunction in OLP by activating the JNK/c-JUN pathway to downregulate Claudin-4, highlighting a novel microbial mechanism contributing to OLP pathogenesis.
CLINICAL RELEVANCE: These findings identify F.n-OMVs as microbial drivers of epithelial barrier disruption in OLP, suggesting that targeting OMVs or the JNK/c-JUN/Claudin-4 axis may offer new diagnostic and therapeutic strategies for OLP management.
METHODS: We utilized single-cell RNA sequencing, spatial transcriptomics, and immunohistochemistry to analyse Claudin-4 expression and its spatial distribution in OLP lesions. In vitro, HaCaT keratinocytes exposed to outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) were evaluated for epithelial barrier function via transepithelial electrical resistance (TEER) and fluorescein isothiocyanate-dextran (FD4) permeability assays. Claudin-4 expression and JNK/c-JUN pathway activation were evaluated by qPCR, Western blotting, and RNA sequencing. The JNK inhibitor SP600125 was used to explore pathway involvement.
RESULTS: Claudin-4 expression was significantly decreased and exhibited disrupted spatial organization in OLP lesions. F.n-OMVs compromised HaCaT epithelial barrier function, downregulated Claudin-4 expression, and altered its localization. Western blotting demonstrated activation of the JNK/c-JUN signaling pathway. Inhibition of JNK with SP600125 restored Claudin-4 expression and barrier function.
CONCLUSION: Our study demonstrates that F.n-OMVs induce epithelial barrier dysfunction in OLP by activating the JNK/c-JUN pathway to downregulate Claudin-4, highlighting a novel microbial mechanism contributing to OLP pathogenesis.
CLINICAL RELEVANCE: These findings identify F.n-OMVs as microbial drivers of epithelial barrier disruption in OLP, suggesting that targeting OMVs or the JNK/c-JUN/Claudin-4 axis may offer new diagnostic and therapeutic strategies for OLP management.