The circRERE/miR-144-3p/TLR2/MMP9 signaling axis in COPD pulmonary monocytes promotes the EMT of pulmonary epithelial cells

Abstract

Chronic obstructive pulmonary disease (COPD) is a serious threat to human health, but an effective targeted therapy for COPD is still lacking at present. During the progression of COPD, the epithelial mesenchymal transition (EMT) ensures the remodeling of pulmonary epithelial cells, and it could not be precisely targeted due to its complex and elusive mechanism. In this study, we determined that the TLR2/MMP9 axis is upregulated in the pulmonary monocytes in cigarette smoke (CS)-induced COPD mice. Using a co-culture system, we identified that the TLR2/MMP9 axis in pulmonary monocytes promotes the EMT of pulmonary epithelial cells. Further, our results confirmed that miR-144-3p inhibits TLR2 expression in monocytes by directly binding to the 3′UTR of TLR2. Finally, we proved that circRERE works as a sponge to antagonize miR-144-3p and promote TLR2 expression in monocytes. Thus, our results conclude that the circRERE/miR-144-3p/TLR2/MMP9 axis in COPD pulmonary monocytes is critical for CS-induced COPD and circRERE may serve as a potential target for COPD.