Aerobic exercise alleviates chronic allergic airway inflammation by regulating the circMETTL9/EIF4A3/IGFBP3 axis.

Abstract

Aerobic exercise has been recommended as a non-pharmacological treatment for asthma. Previous studies have shown that circMETTL9 regulates cellular inflammation, apoptosis, and oxidative stress levels. However, whether aerobic exercise can modulate the expression of circMETTL9 to alleviate chronic allergic airway inflammation remains unclear. In this study, we established a mouse model of chronic allergic lung inflammation with aerobic exercise intervention to assess its effects. Our results demonstrate that aerobic exercise exerts anti-inflammatory, anti-proliferative, anti-apoptotic, and anti-oxidative stress effects by regulating the circMETTL9/EIF4A3/IGFBP3 axis. Mechanistically, we found that circMETTL9 binding to EIF4A3 does not affect EIF4A3 expression. However, EIF4A3 positively regulates both the protein and mRNA levels of IGFBP3. Specifically, circMETTL9 binds to EIF4A3 to inhibit IGFBP3 transcription and translation. This study identifies a novel potential target and research direction for treating chronic allergic lung inflammation.