Adverse outcome pathway of ambient fine particulate matter-induced respiratory toxicity: role of non-coding RNAs

Fine particulate matter (PM_2.5) exposure has been recognized as one of the risk factors for chronic obstructive respiratory disease (COPD). With increased PM_2.5-related research, the mechanism of PM_2.5-induced toxicity suggests the role of non-coding RNA (ncRNA) in this process; however, a comprehensive framework to link PM_2.5 exposure with COPD remains vacant. The adverse outcome pathway (AOP) framework integrates researches from different models to achieve a systematic assessment of PM_2.5 toxicity in the respiratory system. This review focused on PM_2.5-related pathology of COPD at molecular, cellular, organic, individual and population levels using the AOP framework. Combined with our previous studies, the AOP-Wiki website, and other available evidence, we established an AOP framework, in which the molecular initiating event (MIE) is the alteration of ncRNA expression profiles. Subsequently, oxidative stress and activation of inflammation pathway induced pulmonary inflammation, epithelial-mesenchymal transformation (EMT), fibroblast proliferation, and myofibroblast differentiation leading to airway remodeling, pulmonary epithelial cell apoptosis, and autophagy-caused emphysema, were identified as key events (KEs). These key events collectively contribute to the pathogenesis of COPD by altering the structure and function of the airways and lung tissue, thus exacerbating respiratory symptoms and disease progression. This framework will provide a reference to identify biomarkers of PM_2.5 exposure-triggered respiratory diseases.