OSGIN1 regulates PM 2.5 -induced fibrosis via mediating autophagy in an in vitro model of COPD

• Published in: Toxicology letters 2024-11, Vol.401, p.35
• Main Authors: Tang, Xiying, Zhu, Huanhuan, Zhou, Meiyu, Zhang, Huilin, Xiao, Qi, Yuan, Qi, Sun, Guanting, Zhang, Zhengdong, Chu, Haiyan
• Format: Article
• Language: English
• Subjects: Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Autophagy - drug effects; Bronchi - drug effects; Bronchi - metabolism; Bronchi - pathology; Cell Line; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - pathology; Humans; MicroRNAs - genetics; MicroRNAs - metabolism; Particulate Matter - toxicity; Pulmonary Disease, Chronic Obstructive - chemically induced; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - metabolism; Pulmonary Disease, Chronic Obstructive - pathology; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Smoke - adverse effects
• ISSN: 1879-3169
• DOI: 10.1016/j.toxlet.2024.09.003

Fine particulate matter (PM ) has been identified as a significant contributing factor to the exacerbation of chronic obstructive pulmonary disease (COPD). It has been observed that PM may induce lung fibrosis in COPD, although the precise molecular mechanism behind this remains unclear. In a previous study, we demonstrated that PM upregulates oxidative stress induced growth inhibitor 1 (OSGIN1), which in turn leads to injury in airway epithelial cells, thereby, suggesting a potential link between PM exposure and COPD. Based on this, we hypothesized that OSGIN1 plays a role in PM -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 PM 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 PM 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 PM upregulates OSGIN1 through inhibiting miR-654-5p, leading to increased autophagy and fibrosis in CSE-HBEs.