Irisin Ameliorates PM2.5-Induced Acute Lung Injury by Regulation of Autophagy Through AMPK/mTOR Pathway

Abstract

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.

Keywords:

• irisin
• PM2.5
• acute lung injury
• autophagy

Abbreviations

COPD, chronic obstructive pulmonary disease; ALI, acute lung injury; WT, wild-type; BALF, bronchoalveolar lavage fluid; TEM, transmission electron microscopy.

Data Sharing Statement

All data generated or analyzed during this study are available from the corresponding author upon reasonable request.

Ethics Approval

All of the experimental protocols were approved by the Animal Care and Use Committee of the Second Hospital of Hebei Medical University (2022-AE008) China, and in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Acknowledgments

This experiment was carried out at the Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-Cerebrovascular Disease, Shijiazhuang, 050000, Hebei, China.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the Natural Science Foundation of Hebei Province (H2019206263), the Key R&D Program of Hebei Province (19277760D), and the Hebei Province Applied Basic Research Program (15967753D).