BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma

Cell Communication and Signaling

Research

Pei-Pei Cheng¹  Shuai-Jun Chen¹  Qian Li¹  Xiao Feng¹  Yuan-Yi Zheng¹  Meng Wang¹  Hong Ye²  Yi Huang³  Ye-Han Jiang³  Qian Niu³  Li-Qin Zhao³  Li-Mei Liang⁴  Xin-Liang He⁴  Xiaorong Wang⁴  Fei Xiang⁴  Wan-Li Ma⁴  Lin-Jie Song⁴  Fan Yu⁴  Liang Xiong⁴ 

[1] Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, 430030, Wuhan, China;Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, 430030, Wuhan, China;Key Laboratory of Respiratory Diseases, National Health Commission of China, Wuhan, China;Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, 430022, Wuhan, China;Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, 430022, Wuhan, China;Key Laboratory of Respiratory Diseases, National Health Commission of China, Wuhan, China;

关键词: PM2.5;    Asthma;    Remodeling;    BMAL1;    p53;    Autophagy;    Bronchial epithelial cells;   

DOI  :  10.1186/s12964-023-01057-9

 received in 2022-08-08, accepted in 2023-01-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism.ResultsIn this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma.ConclusionsTaken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1.Graphic abstract-uVbdBkq_Y96GVeGRDEcFBVideo Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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