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HOXA1 AND QUERCETIN AS KEY REGULATORS OF AIRWAY EPITHELIAL REGENERATION IN COPD
McCluskey, Elizabeth
McCluskey, Elizabeth
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Thesis/Dissertation
Date
2025-05
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Biomedical Sciences
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https://doi.org/10.34944/3xyc-8w67
Abstract
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airway inflammation, structural remodeling, and impaired epithelial regeneration. The therapeutic potential of quercetin, a naturally occurring flavonoid, and HOXA1, a homeobox gene, in promoting epithelial repair and addressing COPD pathology, are studied. The findings demonstrate that quercetin enhances airway epithelial regeneration by modulating epigenetic mechanisms, promoting proper differentiation, and exerting anti-inflammatory effects. Specifically, quercetin treatment increased transepithelial resistance (TER), restored epithelial integrity, and normalized cell composition by increasing ciliated cells and reducing goblet cell hyperplasia. Furthermore, quercetin reduced pro-inflammatory cytokines, such as IL-6 and IL-8, suggesting its role in mitigating the chronic inflammatory state in COPD.
In parallel, HOXA1's critical role as a regulator of epithelial repair is studied. HOXA1 deficiency was associated with impaired epithelial differentiation, delayed wound healing, and G1/S phase cell cycle arrest. HOXA1 knockout models revealed disrupted epithelial regeneration and abnormal airway structure, emphasizing the gene's importance in maintaining epithelial integrity. HOXA1’s transcriptional regulation is further explored, underscoring a broader regulatory network involved in airway epithelial homeostasis.
Together, these findings suggest a synergistic therapeutic potential of combining quercetin’s multifaceted action with targeted modulation of HOXA1. This dual approach addresses multiple facets of COPD pathology, including inflammation, remodeling, and impaired repair processes. Further exploration of these therapeutic strategies, emphasizing their potential to provide more effective and personalized interventions for COPD and other chronic respiratory diseases is advocated for. These insights pave the way for innovative approaches to improve patient outcomes and quality of life.
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