HMOX1 As a Potential Drug Target for Upper and Lower Airway Diseases: Insights from Multi-omics Analysis

Overview

Journal Respir Res

Date 2025 Jan 28

PMID 39871287

Authors

Enhao Wang

Shazhou Li

Yang Li

Tao Zhou

Affiliations

Soon will be listed here.

Abstract

Background: Oxidative stress is key in inflammatory airway diseases. Heme oxygenase 1 (HMOX1) regulates oxidative stress, but its role in airway diseases needs exploration.

Methods: 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.

Results: 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.

Conclusion: 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.

Clinical Trial: Not applicable.

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