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

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.