Key Takeaways & Executive Findings
- •• BT reduces airway remodeling by suppressing autophagy in human airway smooth muscle cells. • Thermal effects from BT decrease HASMC proliferation and increase apoptosis. • BT inhibits autophagy via downregulation of the AMPK/mTOR signaling pathway. • AMPK agonist or mTOR antagonist reverses BT's effects, confirming pathway involvement.
Abstract
Bronchial thermoplasty (BT), an effective treatment for severe asthma, requires heat to reach the airway to reduce the mass of airway smooth muscle cells (ASMCs). Autophagy is involved in the pathological process of airway remodeling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodeling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study reveal that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence are significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT causes a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increase in temperature significantly downregulates cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulates p62 expression, and inhibits the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolishes the inhibition of autophagy and attenuates the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodeling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.
1. Introduction
Asthma is a lung disease characterized by reversible airway obstruction, airway inflammation, and increased airway responsiveness to multiple stimuli. Severe asthma may cause shortness of breath and chest tightness and may be life-threatening. The main treatment for asthma is drug therapy; however, such treatment can cause side effects and lead to drug tolerance [1–3]. Therefore, identifying nonpharmacological treatments for asthma is important.
Bronchial thermoplasty (BT) is a nondrug procedure that can be used to treat patients with severe persistent asthma, and these patients are unable to effectively control their asthma by the use of corticosteroids and long-acting beta-agonists. BT can reduce acute attacks, exacerbation rates and hospitalization rates and thus improve the quality of life of asthma patients [4–6].
A previous report revealed that BT could reduce airway hyperresponsiveness via the effects of radiofrequency energy [7,8]. It has been reported that thermoplasty may induce epithelial cells to regenerate [9]. Moreover, BT can inhibit fibroblast remodeling by changing the function of epithelial cells [10]. BT is currently believed to exert therapeutic effects by changing the structure or function of airway smooth muscle (ASM) tissue [11], airway nerves [12,13], airway glands [14], and airway vasculature and reducing airway inflammation [15,16]. BT has also been reported to change the function of ASM tissue by diminishing its mass [17]. While silencing of miR-10b-5p was shown to reduce the hypertrophy of human aortic smooth muscle cells (HASMCs) by downregulating FLT1 and upregulating PI3K/Akt [18], the detailed signaling mechanism of BT in asthma has rarely been studied.
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Tao Wang, Peng Fu, Wenting Huang, Liang Long, Fa Long, Shengming Liu (2026). Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway. Acta Biochimica et Biophysica Sinica. https://doi.org/10.3724/abbs.2024028
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Frequently Asked Questions
What is bronchial thermoplasty (BT) and how does it treat severe asthma?
Bronchial thermoplasty is a non-drug procedure that uses heat to reduce the mass of airway smooth muscle cells, thereby decreasing airway hyperresponsiveness and improving asthma control in patients with severe persistent asthma.
How does BT affect autophagy in airway smooth muscle cells?
BT inhibits autophagy in human airway smooth muscle cells, as evidenced by decreased autophagosome formation, reduced LC3II/LC3I ratio and Beclin-1 expression, and increased p62 expression.
What signaling pathway is involved in BT-induced inhibition of autophagy?
The study shows that BT inhibits the AMPK/mTOR signaling pathway, which is crucial for the suppression of autophagy and subsequent reduction of airway remodeling.
What are the clinical implications of this study?
The findings provide mechanistic insights into how BT works, potentially leading to improved therapeutic strategies for severe asthma by targeting autophagy and the AMPK/mTOR pathway.
What methods were used to investigate the effects of BT?
The researchers used airway biopsy tissues from patients and a cell model of human airway smooth muscle cells exposed to increasing temperatures, assessing proliferation, apoptosis, autophagy markers, and signaling pathway activity.
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