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Circadian clock modulates epithelial cell autophagy to alleviate airway inflammation in asthma
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DOI：10.2306/scienceasia1513-1874.2026.039.png)
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Abstract
En 中文
The circadian regulation of autophagy in airway epithelial inflammation remains poorly understood, particularly in the context of asthma. This study investigated how nuclear receptor subfamily 1 group D member 1 (NR1D1)-mediated downregulation of myosin-like BCL2-interacting protein (BECLIN1) influences autophagy in airway epithelial cells to alleviate inflammation. An ovalbumin-induced asthma mouse model and a Beas-2b cell line with type 2 inflammation were established. Rhythmic fluctuations in circadian clock genes (Circadian locomotor output cycles Kaput [Clock], Brain and muscle Arnt-like protein 1 [Bmal1], and Nr1d1) and autophagy-related genes (Autophagy Related 5 [Atg5], Beclin1, and microtubule-associated proteins 1A/1B light chain 3B [Lc3]) were monitored. In vitro, NR1D1 expression was modulated using SR9009 or siRNA, and effects on BECLIN1 and LC3 were assessed. BECLIN1 expression was altered via plasmid transfection to evaluate effects on NR1D1. NR1D1 bonded with and repressed the BECLIN1 promoter. In asthmatic mice and Beas-2b cells, NR1D1 expression was reduced, whereas ATG5, BECLIN1, and LC3 were elevated. CLOCK, BMAL1, NR1D1, ATG5, BECLIN1, and LC3 levels in the lung tissue showed cyclic fluctuations, with NR1D1 and BECLIN1 negatively correlated. SR9009 reduced BECLIN1 and LC3 levels, while NR1D1 knockdown increased them in vitro. BECLIN1 overexpression elevated NR1D1, whereas its inhibition reduced NR1D1. Circadian and autophagy-related genes showed pronounced periodic oscillation in asthmatic mice, coinciding with airway inflammation. NR1D1 negatively regulates BECLIN1 to suppress autophagy and mitigate airway inflammation in asthma, indicating a possible therapeutic target.
Keywords:
circadian clock
autophagy
asthma
airway epithelial cells
BECLIN1
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969
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