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Jiao Ma,1,* Zhuoxiao Han,1,* Rui Jiao,1 Guanli Yuan,1 Cuiqing Ma,2 Xixin Yan,1 Aihong Meng1 1Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, Peopleâs Republic of China; 2Key Laboratory of Immune Mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, Hebei, 050000, Peopleâs Republic of China*These authors contributed equally to this workCorrespondence: Aihong Meng, Department of Respiratory and Critical Care Medicine, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang, Hebei, 050000, Peopleâs Republic of China, Email mengaihong_med@126.comBackground: 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 irisinâs 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.Keywords: irisin, PM2.5, acute lung injury, autophagy |
