鸢尾素通过AMPK/mTOR途径调节自噬改善PM2.5诱导的急性肺损伤。
Irisin Ameliorates PM2.5-Induced Acute Lung Injury by Regulation of Autophagy Through AMPK/mTOR Pathway.
作者信息
Ma Jiao, Han Zhuoxiao, Jiao Rui, Yuan Guanli, Ma Cuiqing, Yan Xixin, Meng Aihong
机构信息
Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.
Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, 050000, People's Republic of China.
出版信息
J Inflamm Res. 2023 Mar 11;16:1045-1057. doi: 10.2147/JIR.S390497. eCollection 2023.
BACKGROUND
PM2.5 exposure is one of the major inducements of various respiratory diseases and related mortality. Meanwhile, irisin, a metabolism and thermogenesis-related hormone, is found to be protective against acute lung injury induced by LPS, which indicates its therapeutic function in lung injury. However, the function and underlying mechanism of irisin in PM2.5-induced acute lung injury (ALI) are still unclear. This study is aimed to discover the potential mechanisms of irisin in PM2.5-induced acute lung injury.
METHODS
Atg5 deficient mice and cells were established to clarify the relationship between irisin and autophagy in PM2.5-induced ALI. We also used Ad-mCherry-GFP-LC3B as a monitor of autophagy flux to claim the effects of irisin on autophagy. Western blotting and qPCR were used to reveal the molecular mechanism.
RESULTS
As a result, PM2.5 exposure induced lung injury whereas mitigated by irisin. Moreover, PM2.5 hampered autophagy flux, characterized by accumulation of p62, and autophagosomes, as well as blocked autolysosomes. Irisin improved the disturbed autophagy flux, which was abrogated by deficiency of Atg5. Additionally, we demonstrated that irisin activated AMPK and inhibited mTOR, which indicated the enhanced autophagy. Moreover, blockage of AMPK by compound C terminated irisin's induction of autophagy in cultured MH-S cells.
CONCLUSION
Our findings reveal that irisin performs protective effects against PM2.5-induced ALI by activating autophagy through AMPK/mTOR signaling pathway.
背景
暴露于细颗粒物（PM2.5）是引发各种呼吸系统疾病及相关死亡的主要诱因之一。同时，鸢尾素作为一种与代谢和产热相关的激素，被发现对脂多糖诱导的急性肺损伤具有保护作用，这表明其在肺损伤中具有治疗功能。然而，鸢尾素在PM2.5诱导的急性肺损伤（ALI）中的作用及潜在机制仍不清楚。本研究旨在探究鸢尾素在PM2.5诱导的急性肺损伤中的潜在机制。
方法
建立自噬相关基因5（Atg5）缺陷的小鼠和细胞模型，以阐明鸢尾素与PM2.5诱导的ALI中自噬之间的关系。我们还使用Ad-mCherry-GFP-LC3B作为自噬通量的监测指标，以明确鸢尾素对自噬的影响。采用蛋白质免疫印迹法和实时荧光定量聚合酶链反应来揭示分子机制。
结果
结果显示，暴露于PM2.5会导致肺损伤，而鸢尾素可减轻这种损伤。此外，PM2.5阻碍了自噬通量，表现为p62和自噬体的积累，以及自噬溶酶体的阻断。鸢尾素改善了紊乱的自噬通量，而Atg5缺陷可消除这种改善作用。此外，我们证明鸢尾素激活了腺苷酸活化蛋白激酶（AMPK）并抑制了雷帕霉素靶蛋白（mTOR），这表明自噬增强。此外，化合物C阻断AMPK可终止鸢尾素在培养的小鼠肺泡巨噬细胞（MH-S）中诱导的自噬。
结论
我们的研究结果表明，鸢尾素通过激活AMPK/mTOR信号通路诱导自噬，从而对PM2.5诱导的ALI发挥保护作用。
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