Asthma has emerged as the most widespread chronic condition in developed nations, impacting more than 10 % of the adult population [1]. Asthma is a persistent inflammatory disorder of the airways, resulting from the interplay of genetic and environmental elements. This interplay manifests as symptoms such as coughing, wheezing, and heightened airway reactivity, along with physiological changes including inflammation, excessive mucus production, angiogenesis, and structural alterations in the airways [2,3]. Airway remodeling, a crucial component alongside inflammation in asthma pathogenesis, is primarily driven by chronic inflammatory cell infiltration and is a significant contributor to refractory asthma, potentially exacerbating subepithelial fibrosis through the enhancement of epithelial–mesenchymal transition (EMT) [[4], [5], [6]]. The plasticity and dynamics of the airway epithelium driven by EMT, underlie the hyperplasia of fibroblasts, goblet cells, and pneumocytes in various lung diseases, contributing to airway remodeling in asthma [7,8]. Further research is ongoing to investigate the mechanisms underlying the development of asthma.

In recent years, exercise training had extended to promoting health, preventing and treating diseases. Exercise had a significant role in inflammatory diseases, with a growing body of research indicating that different intensities of exercise could regulate chronic inflammation [9]. The regular engagement in aerobic exercise (AE) training has proven to be advantageous for allergic asthma management by not only diminishing dyspnea and exercise-induced bronchospasm but also slowing lung function deterioration, lowering exacerbation risk, enhancing aerobic capacity, and elevating the health-related quality of life for patients with allergic asthma [[10], [11], [12]]. Engaging in AE as an intervention enhanced asthma management and quality of life during both the acute and chronic phases [13]. AE mitigated airway hyperresponsiveness in the rat asthma model, with reductions in high mobility group box 1 (HMGB1) and interleukin 17 (IL-17) levels [14]. It was reported that AE suppressed the asthma phenotype induced by house dust mites, a process that involved the regulation of the SOCS-JAK-STAT signaling pathway [15]. Aerobic physical training helped to alleviate the symptoms of severe asthma through its effects on the kinin signaling mechanism [16].

Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs, >200 nucleotides) and microRNAs (miRNAs), had been linked to the pathogenesis of chronic inflammatory and respiratory diseases [17,18]. Especially, many lncRNAs and miRNAs had been reported to have implications for asthma [19,20]. LncRNA MALAT1/miR-155 exhibited the ability to modify the Th1/Th2 balance in asthma by regulating CTLA4 [21]. The lncRNA NEAT1 modulated the Th1/Th2 immune response in pediatric asthma by microRNA-217/GATA3 regulatory pathway [22]. Reducing the levels of lncRNA AK085865 improved asthmatic airway inflammation through the regulation of macrophage polarization [23]. MiR-124-3p served as a key regulator of allergic airway inflammation and structural remodeling in asthma mice triggered by ovalbumin [24]. Epithelial microRNA-30a-3p inhibited airway eosinophilic inflammation in asthma [25].

Our study investigated the levels of HMGB1/RAGE and inflammatory factors in asthmatic mouse models, and the function of aerobic exercise for the lung function in asthmatic mice. The comprehensive bioinformatics analyses and subsequent validation studies indicated that let-7e-5p had binding relationships with both lncRNA P73 antisense RNA 1 (TP73-AS1) and HMGB1. Our preliminary data revealed the regulation of aerobic exercise for TP73-AS1/let-7e-5p/HMGB1 in OVA-induced asthma mouse models was investigated.