MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells.

INTRODUCTION

Bronchial epithelial cell damage is an important determinant of the severity of chronic obstructive pulmonary (COPD). However, the exact molecular mechanisms underlying this cell death in COPD development are not well understood. This study investigates the involvement of microRNA-21 (miR-21/miRNA-21) in COPD and its underlying molecular mechanism.

METHODS

A mouse model of COPD was created by exposing the mice to cigarette smoke (CS) and injecting them with cigarette smoke extract (CSE). Both wild-type mice and miR-21 knockout (miR-21-/-) mice were used to investigate the role of microRNA-21 (miR-21) in exacerbating COPD. Various assays and analyses were performed, including HE staining, tunel staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, quantitative real-time polymerase chain reaction (RT-qPCR), and western blotting (WB) to measure outcomes such as the pathological morphological changes, necroptosis, apoptosis, and levels of inflammatory factors.

RESULTS

Our results revealed an upregulation of miR-21 in the lung tissue of COPD model mice. Additionally, knockout of miR-21 resulted in decreased levels of bronchial epithelial cell necroptosis and apoptosis, as evidenced by the downregulation of tumor necrosis factor receptor 1 (TNFR1), phosphoryl-mixed lineage kinase domain-like protein (p-MLKL) and caspase-3. This downregulation of necroptosis and apoptosis ultimately led to a reduction of inflammatory factors and damage-associated molecular patterns (DAMPs), such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL- 1β), and interleukin-6 (IL-6) and high mobility group protein B1(HMGB1) in the lungs, thereby ameliorating COPD.

CONCLUSIONS

Our findings suggest that miR-21 contributes to the worsening of chronic obstructive pulmonary disease by modulating necroptosis and apoptosis in bronchial epithelial cells, providing a new theoretical basis for the pathogenesis of chronic obstructive pulmonary disease.