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

Abstract

Background

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).

Methods

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.

Results

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.

Conclusion

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.

Keywords:

• COPD
• miR-21
• PTEN/Akt/NF-κB axis
• apoptosis
• inflammation

Data Sharing Statement

All data generated or analyzed during this study are included in this published article.

Ethics Approval and Consent to Participate

The study was approved by the ethical review board of Wuxi People’s Hospital Affiliated to Nanjing Medical University. The ethics approval number was KS2023119 and KS2019008.

Disclosure

Xiaoyan Sai, Chu Qin, and Zixiao Zhang are co-first authors for this study. The authors declare that there is no conflict of interest in this work.

Additional information

Funding

The study was supported by the Project of Nanjing Medical University [grant number NMUB2018357], the Project of Science and Technology Department of Jiangsu Province (No. Z2022087), and the Top Talent Support Program for Young and Middle-Aged People of Wuxi Health Committee (No. BJ2023007).