SOD1-PRDX2-TXN axis protects the nasal epithelial barrier in chronic rhinosinusitis by coordinated antioxidant...

To explore the role of the SOD1-PRDX2-TXN axis in regulating nasal epithelial barrier function in chronic rhinosinusitis (CRS).

Bioinformatic analysis was used to identify CRS-associated mitochondrial function genes. In vitro and in vivo CRS models were established using lipopolysaccharide (LPS). Through overexpression/knockdown of SOD1/PRDX2/TXN, combined with an oxidative stress inducer (H₂O₂), nasal epithelial barrier function, oxidative stress, mitochondrial function, and protein-protein interactions were assessed via H&E/PAS/TUNEL/JC-1 staining, TEER/permeability assays, immunofluorescence, immunohistochemistry, ELISA, Co-IP, and ROS detection. Additionally, we analyzed the expression of SOD1, PRDX2, and TXN in a public clinical transcriptomic dataset (GSE36830).

SOD1 and PRDX2 were identified as core mitochondrial function genes, both downregulated in CRS models, correlating with barrier impairment. In the clinical dataset GSE36830, SOD1 and PRDX2 expression was significantly downregulated in CRS patients. SOD1 overexpression reduced ROS/MDA, increased SOD activity, improved TEER, reduced permeability, restored tight junction protein expression, and decreased apoptosis. H₂O₂ partially reversed these effects. PRDX2 knockdown abolished SOD1's protective effects, increasing ROS/MDA, reducing mitochondrial membrane potential, and worsening barrier function. SOD1 activity was decreased in the CRS mouse model and was restored by SOD1 overexpression, while PRDX2 knockdown reduced SOD1 activity. Co-IP confirmed interactions between SOD1-PRDX2 and PRDX2-TXN. PRDX2 overexpression partially restored LPS-induced TXN downregulation. In PRDX2-knockdown cells, TXN overexpression restored SOD1, PRDX2, and TXN levels, further reduced ROS, MDA, and 4-HNE, and improved barrier function. In vivo, TXN overexpression reduced inflammatory infiltration, goblet cell hyperplasia, and IL-6/IL-18/TNF-α levels, while enhancing antioxidant capacity and barrier integrity. Co-IP confirmed in vivo complex formation among SOD1, PRDX2, and TXN.

SOD1, PRDX2, and TXN may form a functional antioxidant enzyme chain that protects the nasal epithelial barrier in CRS by synergistically reducing oxidative stress, preserving mitochondrial function, and maintaining tight junction integrity. Targeting this axis could offer a new antioxidant therapy strategy for CRS.