FOXM1/LncRNA COPD-R regulates pulmonary inflammation in chronic obstructive pulmonary disease induced by biomass-related PM_2.5

Chronic obstructive pulmonary disease (COPD) is closely associated with biomass fuel (BMF) exposure. Biomass-related PM_2.5 (BRPM_2.5), a fine particulate component of BMF smoke, may contribute to BMF-associated pulmonary inflammation, but the underlying mechanisms remain unclear. This study investigated the role of the FOXM1/lncRNA COPD-R axis in BRPM_2.5-induced pulmonary inflammatory responses. A BMF-induced COPD rat model was established, followed by lung tissue RNA sequencing. Rat L2 cells were treated with lncRNA COPD-R knockdown or overexpression with or without BRPM_2.5 exposure. qPCR, FISH, Western blotting, ELISA, ChIP, and dual-luciferase reporter assays were performed to assess lncRNA COPD-R expression, localization, inflammatory responses and transcriptional regulation. After 7 months of BMF exposure in rats, 312 differentially expressed lncRNAs were identified, including 294 upregulated and 18 downregulated transcripts. lncRNA COPD-R expression increased from 0.1505 ± 0.04259 in controls to 1.054 ± 0.2983 in the BMF group (P < 0.01). RNA sequencing of L2 cells following lncRNA COPD-R knockdown revealed enrichment of differentially expressed genes in the IL-17 and other inflammatory signaling pathways. Transcription factor prediction, ChIP and dual-luciferase assays supported FOXM1-mediated transcriptional regulation of lncRNA COPD-R through promoter binding. BRPM_2.5 increased lncRNA COPD-R expression, whereas lncRNA COPD-R knockdown reduced BRPM_2.5-induced CCL2, IL-17F, MMP-9 and TIMP-1 expression. FOXM1 knockdown or overexpression affected lncRNA COPD-R expression and inflammatory responses, whereas lncRNA COPD-R overexpression rescued these effects following FOXM1 knockdown. Collectively, our findings provide new insights into the mechanisms underlying BRPM_2.5-induced pulmonary inflammation and suggest that the FOXM1/lncRNA COPD-R axis may play an important role in this process.