PBX3 regulates mast cell parthanatos via TOP2A mediated DNA damage in allergic rhinitis

This study explores the regulatory roles of TOP2A and PBX3 in mast cell sensitization and allergic rhinitis (AR). We induced mast cell differentiation from Balb/c mouse bone marrow cells via IL-3 and SCF, and found markedly increased TOP2A expression. TOP2A plays a key role in mast cell parthanatos, survival, mitochondrial function, and degranulation. Overexpression enhanced cell survival, reduced apoptosis, and maintained mitochondrial membrane potential (MMP), while knockdown reversed these effects. Additionally, TOP2A regulates DNA damage, senescence, and inflammation, particularly PARP-1 expression linked to DNA damage. To explore its upstream regulation, we found that PBX3 directly binds to the TOP2A promoter to regulate transcription. High PBX3 expression correlates closely with aggravated AR symptoms, while PBX3 knockdown significantly alleviated AR symptoms in mice, including reduced sneezing, nose rubbing, nasal discharge, and decreased infiltration of inflammatory cells, eosinophils, and mast cells. In conclusion, PBX3 plays an important role in regulating TOP2A expression, DNA damage, cell senescence, inflammation, and mitochondrial function, making it a potential target for AR treatment.