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

• Published in: Acta biochimica et biophysica Sinica 2024-05, Vol.56 (5), p.730-739
• Main Authors: Wang, Tao, Fu, Peng, Huang, Wenting, Long, Liang, Long, Fa, Liu, Shengming
• Format: Article
• Language: English
• Subjects: Airway Remodeling; Aminoimidazole Carboxamide - analogs & derivatives; AMP-Activated Protein Kinases - metabolism; AMPK/mTOR; apoptosis; Apoptosis - drug effects; Asthma - metabolism; Asthma - pathology; autophagy; Autophagy - drug effects; Bronchi - metabolism; Bronchi - pathology; bronchial thermoplasty; Bronchial Thermoplasty - methods; Cell Proliferation - drug effects; Cells, Cultured; Humans; Male; Myocytes, Smooth Muscle - metabolism; Ribonucleotides; Signal Transduction; TOR Serine-Threonine Kinases - metabolism
• ISSN: 1672-9145; 1745-7270; 1745-7270
• DOI: 10.3724/abbs.2024028

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.