Aerobic exercise activates let-7e-5p through TP73-AS1 to inhibit the HMGB1/RAGE axis and alleviate asthma airway inflammation and remodeling

Dan Wang; Jing Zhao; Chunyan Yang; Daogang Qin; Dengna Zhu

doi:10.1016/j.cellimm.2025.104990

Aerobic exercise activates let-7e-5p through TP73-AS1 to inhibit the HMGB1/RAGE axis and alleviate asthma airway inflammation and remodeling

Cell Immunol. 2025 Jun 7:414:104990. doi: 10.1016/j.cellimm.2025.104990. Online ahead of print.

Authors

Dan Wang¹, Jing Zhao², Chunyan Yang², Daogang Qin², Dengna Zhu³

Affiliations

¹ Department of Rehabilitation Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, China; Department of Pediatric, Liaocheng People's Hospital, Liaocheng 252004, Shandong Province, China.
² Department of Pediatric, Liaocheng People's Hospital, Liaocheng 252004, Shandong Province, China.
³ Department of Rehabilitation Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, China; Henan Key Laboratory of Child Brain Injury and Henan Pediatric Clinical Research Center, Institute of Neuroscience and Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan province, PR China. Electronic address: zhudengna@126.com.

PMID: 40499319
DOI: 10.1016/j.cellimm.2025.104990

Abstract

The rising incidence of asthma, a chronic respiratory condition, has been associated with the involvement of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in its pathogenesis. Nevertheless, there is a shortage of data pertaining to the impact of lncRNA TP73-AS1 and let-7e-5p on this disease. Therefore, we aimed to explore the possible effects of aerobic exercise (AE) on lncRNA TP73-AS1, let-7e-5p, inflammation, and high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) in asthma mouse models. HMGB1/RAGE was significantly upregulated in asthma mouse models using ovalbumin (OVA) stimulation. The overexpression of let-7e-5p, which was found to be significantly downregulated in asthma mouse models, appeared to inhibit EMT and might alleviate airway inflammation in asthmatic mice through the suppression of the HMGB1/RAGE pathway. Aerobic exercise was associated with reduced airway inflammation and remodeling in asthmatic mice, and appeared to suppress TP73-AS1 expression in asthma OVA-mouse models. Furthermore, TP73-AS1 may exacerbate airway inflammation and remodeling in OVA-induced asthmatic mice by downregulating let-7e-5p expression, which could activate the HMGB1/RAGE-NF-κB pathway. These findings suggest potential innovative approaches for asthma management, which warrant further validation.

Keywords: Aerobic exercise; Asthma; HMGB1/RAGE; Let-7e-5p; TP73-AS1.