Nuclear Factor Erythroid 2-Related Factor 2 in Chronic Obstructive Pulmonary Disease Progression: Regulation of Macrophage Polarization and Hyaluronic Acid Metabolism
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Le résumé fourni par la source
Background: Alveolar microenvironment-driven macrophage polarization critically influences chronic obstructive pulmonary disease (COPD) progression. Nuclear factor erythroid 2-related factor 2 (NRF2), a key transcription factor, regulates macrophage polarization, suppresses inflammation, and promotes cellular repair. However, its role in macrophage-mediated inflammation and metabolic regulation, particularly hyaluronic acid (HA)-related remodeling, remains incompletely defined. This study investigates a novel dimension of NRF2 in COPD pathogenesis through macrophage-specific modulation, aiming to uncover its previously unrecognized mechanism. Methods: knockout (KO) and control mice were chronically exposed to cigarette smoke (CS) to induce COPD-like pathology. Lung function, alveolar damage, macrophage polarization (M1/M2), and inflammatory cytokines were analyzed by respiratory function tests, histology, immunohistochemistry, and chemokine profiling, respectively. Proteomics approaches were used to identify dysregulated pathways. Results: KO mice displayed aggravated CS-induced lung dysfunction and alveolar destruction compared with control mice, accompanied by heightened M1 polarization and elevated pro-inflammatory cytokines (C-C motif chemokine ligand [CCL]2, CCL7, CXCL16). Proteomics revealed dysregulation of immune, oxidative stress, and metabolic pathways in the lungs of KO mice, including HA metabolism/uptake-associated proteins and increased CD44/CD74 expression. These findings suggest an association between NRF2 deficiency, macrophage polarization imbalance, and HA-related remodeling. Conclusion: Macrophage-specific NRF2 protects against CS-induced COPD-like lung injury by restraining inflammatory activation and preserving macrophage polarization-associated balance. Proteomic and validation analyses further nominate HA metabolism-related remodeling, particularly the CD44/CD74-associated response, as a biologically plausible feature of NRF2-deficient disease progression. These findings define a macrophage NRF2-linked inflammatory-remodeling axis in COPD-like pathology while highlighting the need for functional studies to establish whether HA/CD44 signaling is a causal downstream mechanism.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Nuclear Factor Erythroid 2-Related Factor 2 in Chronic Obstructive Pulmonary Disease Progression: Regulation of Macrophage Polarization and Hyaluronic Acid Metabolism
- Date Crossref
- 01/08/2026
- Éditeur
- Informa UK Limited
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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First Affiliated Hospital of Guangzhou Medical University State Key Laboratory of Respiratory Diseases pays non établi dans la noticeÉtablissement de santé
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State Key Laboratory of Respiratory Disease pays non établi dans la noticeStructure de recherche
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Guangzhou Institute of Respiratory Health pays non établi dans la noticeStructure de recherche
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Guangzhou Medical University pays non établi dans la noticeUniversité ou école supérieure
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Ningxia Medical University Department of Pulmonary and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
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Guangzhou Women and Children Medical Center pays non établi dans la noticeÉtablissement de santé
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GMU-GIBH Joint School of Life Sciences pays non établi dans la noticeUniversité ou école supérieure
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Guangzhou National Laboratory pays non établi dans la noticeStructure de recherche
State Key Laboratory of Respiratory Diseases — First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease et Guangzhou Institute of Respiratory Health, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.