Differential Expression of Antioxidant and Oxidant Pathways in Chronic Rhinosinusitis Without Nasal Polyps

TL;DR

This study identifies unique redox gene expression patterns in chronic rhinosinusitis without nasal polyps, showing increased oxidative stress and distinct differences compared to cases with nasal polyps.

Contribution

The study provides a systematic transcriptomic analysis of redox gene expression in CRSsNP, revealing unique antioxidant and oxidant pathway differences compared to CRSwNP.

Findings

27 redox genes were differentially expressed in CRSsNP, with 24 upregulated and 3 downregulated.

CRSsNP showed a significant increase in oxidative stress compared to controls.

CRSsNP and CRSwNP had 16 unique redox differentially expressed genes, indicating distinct pathophysiological mechanisms.

Abstract

Chronic rhinosinusitis without nasal polyps (CRSsNP) is a chronic inflammatory disease that lacks a clear pathogenesis/pathophysiology. While large studies focused on elucidating the pathophysiology of CRS with NPs (CRSwNP), this study aimed to use a systemic evaluation approach to identify the redox gene expression profile, its association with oxidative damage in CRSsNP, and the differences between CRSsNP and -wNP. The expression of 84 redox genes was analyzed using real-time PCR array in control and CRSsNP nasal mucosae. Changes in the mRNA and protein levels of these redox differentially expressed genes (DEGs) were verified using a customized real-time PCR array, RT-PCR, and Western blotting in an additional 18 patients. 4-Hydroxynonenal (lipid peroxidation) and 3-nitrotyrosine (protein nitrosylation) expression, representing oxidative stress (OxS) and nitrosative stress (NsS) status, were examined using immunohistochemistry. We found 27 DEGs (24 upregulated and 3 downregulated) in CRSsNP. AKR1C2, GCLM, GPX2, NOS2, and NQO1 were upregulated and LPO was downregulated more than 4-fold. These changes led to a substantial increase in OxS in CRSsNP nasal mucosa. In a comparison of the currently identified 27 DEGs with the 23 previously reported CRSwNP genes, there were 16 unique redox DEGs expressed between CRSsNP and -wNP. A String protein interaction network analysis revealed that CRSsNP possessed “an adaptive antioxidant defense signature”, while CRSwNP showed “a pro-inflammatory and -oxidant pathway”. Collectively, we systemically performed transcriptomic analysis to profile OxS-related genes in CRSsNP and highlighted the unique redox gene sets and pathway differences between CRSsNP and -wNP.

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