Bronchial thermoplasty decreases airway remodeling by inhibiting autophagy via the AMPK/mTOR signaling pathway

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 remodelling in patients with asthma. However, it remains unclear whether autophagy participates in controlling airway remodelling induced by BT. In this study, we aim to elucidate the autophagy-mediated molecular mechanisms in BT. Our study revealed that the number of autophagosomes and the level of alpha-smooth muscle actin (α-SMA) fluorescence were significantly decreased in airway biopsy tissues after BT. As the temperature increased, BT caused a decrease in cell proliferation and a concomitant increase in the apoptosis of human airway smooth muscle cells (HASMCs). Furthermore, increases in temperature significantly downregulated cellular autophagy, autophagosome accumulation, the LC3II/LC3I ratio, and Beclin-1 expression, upregulated p62 expression, and inhibited the AMPK/mTOR pathway. Furthermore, cotreatment with AICAR (an AMPK agonist) or RAPA (an mTOR antagonist) abolished the inhibition of autophagy and attenuated the increase in the apoptosis rate of HASMCs induced by the thermal effect. Therefore, we conclude that BT decreases airway remodelling by blocking autophagy induced by the AMPK/mTOR signaling pathway in HASMCs.