Exercise's protective role in chronic obstructive pulmonary disease via modulation of M1 macrophage phenotype through...

ObjectiveChronic obstructive pulmonary disease is a leading cause of global mortality. Although exercise training improves lung function and quality of life in chronic obstructive pulmonary disease patients, its mechanisms remain unclear. This study aims to reveal the effects of exercise on chronic obstructive pulmonary disease and elucidate the underlying molecular mechanisms involved.MethodsThis pre-post observational cohort study included 11 chronic obstructive pulmonary disease patients who underwent a 12-week exercise training program to evaluate the effects of exercise intervention. A cigarette smoke-induced chronic obstructive pulmonary disease mouse model and a cigarette smoke extract-induced bronchial endothelial cell model were utilized to investigate the protective mechanisms of exercise. Next-generation sequencing, bioinformatics analyses, luciferase reporter assays, and RT-qPCR were employed to assess mRNA and miRNA expression levels and correlation. Bioinformatics analysis and luciferase reporter assays were performed to identify direct downstream targets of miR-124-3p.ResultsExercise ameliorated lung inflammation in chronic obstructive pulmonary disease mouse lung tissue and human peripheral blood leucocytes. It inhibited M1 macrophage activation in response to cigarette smoke extract and led to the upregulation of miR-124-3p expression. Overexpression of miR-124-3p attenuated cigarette smoke extract-induced lung injury and inflammatory responses. Luciferase reporter assays identified endoplasmic reticulum to nucleus signaling 1 as a direct downstream target of miR-124-3p, and endoplasmic reticulum to nucleus signaling 1 overexpression reversed the anti-inflammatory effects mediated by miR-124-3p.ConclusionsExercise improved patient endurance and alleviated emphysema-related inflammation. It increased miR-124-3p expression, which inhibited the M1 macrophage phenotype and attenuated smoking-related lung injury by targeting endoplasmic reticulum to nucleus signaling 1.