Research articles
ScienceAsia 52 (2026):ID 2026039 1-12 |doi:
10.2306/scienceasia1513-1874..039
Circadian clock modulates epithelial cell autophagy to
alleviate airway inflammation in asthma
Lei Zhanga,b, Zhou Jianga,*, Hanmin Liua,c,d,*, ShuTing Chenga, Xing Zuoa
ABSTRACT: 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.
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| a |
NHCKeyLaboratory of Chronobiology (Sichuan University), Chengdu 610041 China |
| b |
Department of Pediatric Chengdu Women?s and Children?s Central Hospital, School of Medicine, University of
Electronic Science and Technology of China, Chengdu, Sichuan 610017China |
| c |
Department of Pediatric Pulmonology and Immunology, West China Second University Hospital, Sichuan University,
Chengdu 610041 China |
| d |
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), West China
Second University Hospital, Ministry of Education, Sichuan 610041 China |
* Corresponding author, E-mail: Jiang-yuqian@126.com, liuhm@scu.edu.cn
Received 16 Sep 2025, Accepted 14 Apr 2026
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