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Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway
Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway
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Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway
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Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway
Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway
Journal Article

Melatonin: a promising therapy to combat type 2 airway inflammation via MT1-Sirt1 pathway

2026
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Overview
Type 2 asthma is characterized by airway inflammation, mucus hypersecretion, and remodeling, and circadian rhythm dysregulation is implicated in its pathogenesis. Melatonin, a key circadian hormone, modulates inflammatory signaling, but its role in type 2 airway inflammation remains unclear. This study investigated whether melatonin alleviates airway inflammation and epithelial-mesenchymal transition (EMT) through the melatonin receptor 1 (MT1)-Sirtuin 1 (Sirt1) signaling pathway and circadian clock regulation. An ovalbumin (OVA)-induced mouse model of type 2 airway inflammation and cultured airway epithelial cells were used. Lung structural remodeling and mucus production were evaluated using hematoxylin and eosin, Masson's trichrome, and periodic acid-Schiff staining. Airway inflammation was assessed by differential inflammatory cell counts in bronchoalveolar lavage fluid. The mRNA and protein expression of circadian clock genes (CRY1 and PER1) and key components of the MT1-Sirt1 pathway were assessed by quantitative real-time PCR, Western blotting, and immunohistochemistry. EMT-related markers were further examined to explore downstream mechanisms. Melatonin treatment activated MT1-Sirt1 signaling and reduced the expression of circadian clock genes CRY1 and PER1. These effects were accompanied by decreased airway inflammation, reduced mucus production, and attenuation of epithelial-mesenchymal transition (EMT) in airway epithelial cells, all of which reached statistical significance. Our findings identify a novel MT1-Sirt1-circadian gene regulatory axis through which melatonin mitigates type 2 airway inflammation and airway remodeling. These results highlight the therapeutic potential of melatonin for type 2 asthma. Limitations include the use of a single animal model and analysis at a single time point.