Peroxiredoxin 2 Alleviates Oxidative Stress-Induced Epithelial Remodeling in Chronic Rhinosinusitis with Nasal Polyps

Abstract

Objective

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a chronic inflammatory disease characterized by epithelial remodeling. This study aimed to investigate the role of peroxiredoxin 2 (PRDX2) in CRSwNP and its potential mechanisms.

Methods

Proteomics analysis was conducted on nasal tissues from CRSwNP patients and healthy controls. Top-rank differentially expressed proteins were validated by immunofluorescence (IF) staining and reverse transcription quantitative-polymerase chain reaction (RT-PCR). In vitro experiments validated the effects and regulatory mechanisms of PRDX2 on nasal epithelial remodeling.

Results

Proteomics results revealed a disease-specific protein expression profile in CRSwNP polyp tissues, with DEGs primarily associated with oxidative stress. Our validation results demonstrated elevated reactive oxygen species (ROS) levels in CRSwNP with predominant accumulation in the nasal epithelium. Among these DEGs, PRDX2 was the most significantly downregulated, which was further confirmed by RT-PCR and IF. Moreover, PRDX2 was primarily expressed in nasal epithelial cells (NECs). RT-PCR results indicated that tissue PRDX2 expression was positively correlated with E-cadherin and negatively correlated with TGF-β1 and Vimentin expression in CRSwNP. In vitro experiments demonstrated that H₂O₂ stimulation promoted ROS and epithelial-mesenchymal transition (EMT) in NECs, while PRDX2 overexpression (OE) mitigated these effects. Furthermore, PRDX2 OE suppressed the H₂O₂-induced activation of the TGF-β1/SMAD signaling pathway, which plays a crucial role in regulating EMT in NECs.

Conclusion

Our findings suggest that the accumulation of ROS plays a critical role in the pathogenesis of CRSwNP. PRDX2 modulates ROS-induced epithelial remodeling, contributing to disease progression by activating the TGF-β1/Smad signaling pathway.