Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress—which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)—were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.

中文翻译：

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慢性鼻窦炎鼻息肉患者氧化应激相关基因的转录组学分析：识别与鼻息肉有关的新基因

慢性鼻窦炎伴鼻息肉（CRSwNP）是一种复杂的炎症性疾病，其潜在机制尚不清楚。虽然据报道一些活性氧/氮物种相关基因产物参与 CRSwNP，但对 CRSwNP 中氧化应激相关基因的系统和全面分析尚未得到广泛研究。因此，本研究试图对对照和 CRSwNP 患者中与氧化应激和抗氧化防御相关的基因表达模式进行分类。总共招募了 25 名对照和 25 名 CRSwNP 患者。作为氧化应激标志物的 4-羟基壬烯醛和 3-硝基酪氨酸的分布和表达——以 CRSwNP 鼻息肉 (NPs) 中的脂质过氧化和酪氨酸残基的蛋白质硝化为代表——比对照鼻息肉中发现的那些更明显增加。通过免疫组织化学 (IHC) 测定。实时荧光定量PCR分析84个氧化应激相关基因在鼻黏膜和NP组织中的表达，分别有19个基因和4个基因显着上调和下调；其中，诱导型一氧化氮合酶 (iNOS) 和血红素加氧酶 1 (HO-1) 显着上调，而乳过氧化物酶 (LPO)、髓过氧化物酶 (MPO) 和超氧化物歧化酶 3 (SOD3) 高度下调。这些氧化还原蛋白的 mRNA 和蛋白质水平的变化通过定制的实时 PCR 阵列和 RT-PCR 分析以及蛋白质印迹和 IHC 分析得到证实。接受者操作特征曲线分析进一步表明 LPO、MPO、SOD3、HO-1 和 iNOS 可能是 CRSwNP 发展的内型预测因子。总的来说，我们提出了 CRSwNP NP 组织的氧化应激相关基因谱，提供了证据表明氧化应激和抗氧化防御系统的系统性变化，包括新的 iNOS、血红素过氧化物酶和其他基因，与 CRSwNP 病理学密切相关，发展，进步。和 iNOS 可能是 CRSwNP 发展的内型预测因子。总的来说，我们提出了 CRSwNP NP 组织的氧化应激相关基因谱，提供了证据表明氧化应激和抗氧化防御系统的系统性变化，包括新的 iNOS、血红素过氧化物酶和其他基因，与 CRSwNP 病理学密切相关，发展，进步。和 iNOS 可能是 CRSwNP 发展的内型预测因子。总的来说，我们提出了 CRSwNP NP 组织的氧化应激相关基因谱，提供了证据表明氧化应激和抗氧化防御系统的系统性变化，包括新的 iNOS、血红素过氧化物酶和其他基因，与 CRSwNP 病理学密切相关，发展，进步。