RGS1 induces nasal epithelial barrier dysfunction in allergic rhinitis by modulating NF-κB/AQP5 axis.

The tight junctions (TJs) between nasal mucosal epithelial cells are a crucial component of the nasal barrier function. Incomplete formation or reduced expression of TJs is a primary contributor to the onset and progression of allergic rhinitis (AR). Therefore, an in-depth investigation into the mechanisms affecting the barrier function of human nasal mucosal epithelial cells (HNEpCs) may facilitate the identification of new therapeutic approaches for AR treatment. Bioinformatics analysis found RGS1 is upregulated in AR, but its impact on the nasal mucosal epithelial barrier function remains unclear. This study aims to explore the mechanism of RGS1 regulating epithelial barrier function in AR. Differentially expressed genes in AR were analyzed using GSE43523 from GEO database. RGS1 expression level was validated in AR clinical samples and IL-13-induced HNEpCs. Loss and function of RGS1 or/and AQP5 was performed in IL-13-induced HNEpCs to detect the activation of NF-κB signal pathway. The epithelial barrier function of HNEpCs was measured by trans-epithelial electrical resistance (TER) and FITC-Dextran 4(FD4) assay. TJs, such as ZO-1, Occludin and Claudin-1 were also detected by western blot and Immunofluorescence. Bioinformatics analysis, AR clinical samples and IL-13-induced HNEpCs consistently found up-regulated RGS1 expression in AR. RGS1 silencing can protect HNEpCs against IL-13-induced epithelial barrier dysfunction, evidence by increased TER value, decreased FD4 and elevated expression of ZO-1, Occludin and Claudin-1. RGS1 silencing can also suppress the activation of NF-κB signal pathway and increase AQP5 expression, which such expression pattern can be nullified in response to AQP5 silencing. RGS1 was found to be elevated in AR. Silencing of RGS1 can suppress NF-κB signal pathway to increase AQP5 expression, thereby attenuating epithelial barrier dysfunction in HNEpCs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-025-00825-4.