PDF(Pubmed)
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.
摘要：
支气管热成形术(BT),对严重哮喘的有效治疗,需要热量到达气道以减少气道平滑肌细胞（ASMC）的质量。自噬参与哮喘患者气道重塑的病理过程。然而,目前尚不清楚自噬是否参与控制BT诱导的气道重塑。在这项研究中,我们旨在阐明BT中自噬介导的分子机制。我们的研究表明，BT后气道活检组织中自噬体的数量和α-平滑肌肌动蛋白（α-SMA）荧光水平显着降低。随着温度的升高,BT引起人气道平滑肌细胞（HASMC）的细胞增殖减少和伴随的凋亡增加。此外，温度升高显著下调细胞自噬，自噬体积累，LC3II/LC3I比值，和Beclin-1表达式，上调p62表达，并抑制AMPK/mTOR通路。此外，与AICAR（AMPK激动剂）或RAPA（mTOR拮抗剂）共同治疗可消除自噬的抑制作用，并减弱由热效应诱导的HASMC凋亡率的增加。因此,我们得出结论，BT通过阻断HASMC中AMPK/mTOR信号通路诱导的自噬来减少气道重塑。
