A miRNA-21-Mediated PTEN/Akt/NF-κB Axis Promotes Chronic Obstructive Pulmonary Disease Pathogenesis

• Published in: International journal of chronic obstructive pulmonary disease Vol. 19; pp. 1141 - 1151
• Main Authors: Sai, Xiaoyan, Qin, Chu, Zhang, Zixiao, Yu, Haoda, Bian, Tao
• Format: Journal Article
• Language: English
• Published: New Zealand Dove 01.01.2024; Dove Medical Press
• Subjects: A549 Cells; Aged; Animals; Apoptosis; Cigarette Smoking - adverse effects; copd; Disease Models, Animal; Female; Humans; inflammation; Inflammation Mediators - metabolism; Interleukin-6 - metabolism; Interleukin-8 - metabolism; Lung - metabolism; Lung - pathology; Male; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; mir-21; NF-kappa B - metabolism; Original Research; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; pten/akt/nf-κb axis; Pulmonary Disease, Chronic Obstructive - genetics; Pulmonary Disease, Chronic Obstructive - pathology; Signal Transduction; apoptosis; miR-21; inflammation; COPD; PTEN/Akt/NF-κB axis
• ISSN: 1178-2005; 1176-9106; 1178-2005
• DOI: 10.2147/COPD.S453593

This study sought to explore the underlying mechanism of miR-21 mediated apoptosis and inflammation in chronic obstructive pulmonary disease (COPD) induced by cigarette smoke (CS). We detected levels and PTEN/Akt/NF-κB axis protein levels in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Western blotting assay was used to determine the expression of cleaved caspase-3. IL-6 and IL-8 protein was detected in cell supernatant from cells by ELISA. HBE cells were transfected with a miR-21 inhibitor, and co-culture with A549. Increased miR-21 expression, reduced PTEN expression and following activation of Akt in in peripheral lung tissues of COPD patients and CS-exposed mice and HBE cells. Inhibition of miR-21 showed enhanced PTEN levels and reduced the expression of phosphorylated form of Akt and NF-κB. Decreased expression of cleaved caspase-3, IL-6 and IL-8 in A549 cells co cultured with HBE cells transfected with miR-21 inhibitor compared with transfected with miR-21 control inhibitor. MiR-21 contributes to COPD pathogenesis by modulating apoptosis and inflammation through the PTEN/Akt/NF-κB pathway. Targeting miR-21 may increase PTEN expression and inhibit Akt/NF-κB pathway, offering potential diagnostic and therapeutic value in COPD management.