OSGIN1 regulates PM2.5-induced fibrosis via mediating autophagy in an in vitro model of COPD.

Fine particulate matter (PM2.5) has been identified as a significant contributing factor to the exacerbation of chronic obstructive pulmonary disease (COPD). It has been observed that PM2.5 may induce lung fibrosis in COPD, although the precise molecular mechanism behind this remains unclear. In a previous study, we demonstrated that PM2.5 upregulates oxidative stress induced growth inhibitor 1 (OSGIN1), which in turn leads to injury in airway epithelial cells, thereby, suggesting a potential link between PM2.5 exposure and COPD. Based on this, we hypothesized that OSGIN1 plays a role in PM2.5-induced fibrosis in COPD. Human bronchial epithelial cells (HBEs) were treated with cigarette smoke extract (CSE) to construct an in vitro model of COPD. Our findings revealed that PM2.5 increased fibrosis indicators and upregulated OSGIN1 in CSE-stimulated HBEs (CSE-HBEs), and knockdown of OSGIN1 reduced the expression of fibrosis indicators. Through the use of microRNA target prediction software and the Gene Expression Omnibus database, we predicted miRNAs that targeted OSGIN1 in COPD. Subsequently, real-time polymerase chain reaction and western blot analysis confirmed that PM2.5 modulated miR-654-5p to regulate OSGIN1 in CSE-HBEs. Western blot demonstrated that OSGIN1 induced autophagy, thereby exacerbating fibrosis in CSE-HBEs. In summary, our results suggest that PM2.5 upregulates OSGIN1 through inhibiting miR-654-5p, leading to increased autophagy and fibrosis in CSE-HBEs.