Wang Enhao, Li Shazhou, Li Yang, Zhou Tao
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.
Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Respir Res. 2025 Jan 27;26(1):41. doi: 10.1186/s12931-025-03124-w.
Oxidative stress is key in inflammatory airway diseases. Heme oxygenase 1 (HMOX1) regulates oxidative stress, but its role in airway diseases needs exploration.
Differentially expressed genes (DEGs) between healthy nasal mucosa and chronic rhinosinusitis with nasal polyps (CRSwNP) were identified from Gene Expression Omnibus (GEO). Candidate genes were further screened using Gene Set Enrichment Analysis (GSEA) and Random Forest (RF) algorithms. Causal inference between candidate genes and upper and lower airway diseases (CRSwNP, allergic rhinitis (AR), and asthma (AS)) was conducted using bidirectional two-sample Mendelian randomization (TwoSampleMR) analysis. Single-cell RNA sequencing (scRNA-seq) data were used to determine the cellular localization and intercellular interactions of candidate genes. Molecular docking was used to identify potential therapeutic agents.
HMOX1 expression was significantly elevated in CRSwNP. TwoSampleMR analysis indicated a negative causal relationship between HMOX1 exposure and the occurrence of upper and lower airway diseases (CRSwNP [(odds ratio (OR)/95% confidence interval (CI): 0.945/(0.893-0.999), P = 0.044], AR [OR/95% CI: 0.997/(0.994-0.999), P = 0.007], and AS [OR/95% CI: 0.935/(0.895-0.977), P = 0.003]). scRNA-seq data revealed HMOX1 localization in M2 macrophages. Molecular docking identified 15 antioxidants, including Acetylcysteine and Quercetin, that can upregulate HMOX1 expression.
HMOX1 may have a protective role in the pathogenesis of upper and lower airway diseases (CRSwNP, AR, and AS) by modulating oxidative stress. Antioxidants that increase HMOX1 expression could offer new therapeutic avenues for these diseases.
Not applicable.
氧化应激在炎症性气道疾病中起关键作用。血红素加氧酶1（HMOX1）调节氧化应激，但其在气道疾病中的作用尚需探索。
从基因表达综合数据库（GEO）中鉴定健康鼻黏膜与伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）之间的差异表达基因（DEG）。使用基因集富集分析（GSEA）和随机森林（RF）算法进一步筛选候选基因。采用双向双样本孟德尔随机化（TwoSampleMR）分析对候选基因与上、下气道疾病（CRSwNP、过敏性鼻炎（AR）和哮喘（AS））之间进行因果推断。利用单细胞RNA测序（scRNA-seq）数据确定候选基因的细胞定位和细胞间相互作用。采用分子对接来鉴定潜在的治疗药物。
CRSwNP中HMOX1表达显著升高。TwoSampleMR分析表明，HMOX1暴露与上、下气道疾病的发生呈负因果关系（CRSwNP [比值比（OR）/95%置信区间（CI）：0.945/（0.893 - 0.999），P = 0.044]，AR [OR/95% CI：0.997/（0.994 - 0.999），P = 0.007]，AS [OR/95% CI：0.935/（0.895 - 0.977），P = 0.003]）。scRNA-seq数据显示HMOX1定位于M2巨噬细胞。分子对接鉴定出15种抗氧化剂，包括乙酰半胱氨酸和槲皮素，它们可上调HMOX1表达。
HMOX1可能通过调节氧化应激在上、下气道疾病（CRSwNP、AR和AS）的发病机制中发挥保护作用。增加HMOX1表达的抗氧化剂可为这些疾病提供新的治疗途径。
不适用。
