International Journal of COPD (Apr 2023)
MicroRNA Let-7 Induces M2 Macrophage Polarization in COPD Emphysema Through the IL-6/STAT3 Pathway
Abstract
Tingting Liu, Zheming Zhang, Weiyu Shen, Yan Wu, Tao Bian Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of ChinaCorrespondence: Tao Bian; Yan Wu, Department of Respiratory Medicine, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China, Email [email protected]; [email protected]: M2 polarized macrophages are involved in the occurrence and development of emphysema in COPD patients. However, the molecular mechanism of M2 macrophage polarization is still unclear. This study investigated the molecular mechanism of let-7 differentially expressed in bronchial epithelial cells of COPD patients participating in COPD emphysema by regulating the expression of IL-6 and inducing M2 polarization of alveolar macrophages (AM).Materials and Methods: We measured let-7c expression in human lung tissue, serum and the lung tissue of cigarette smoke (CS)-exposed mice by qRT‒PCR. We observed the M1/M2 AM polarization in the lungs of COPD patients and COPD model mice by immunofluorescence analysis. Western blotting was used to determine the expression of MMP9/12 in the lung tissue of COPD patients and CS-exposed mice. An in vitro experiment was performed to determine the molecular mechanism of let-7c-induced macrophage polarization.Results: Let-7c expression was downregulated in COPD patients, CS-exposed mice, and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. AMs in COPD patients and CS-exposed mice were dominated by the M2 type, and the release of MMP9/12 was increased. In vitro, the transfection of mimics overexpressing let-7 or the use of tocilizumab to block signal transduction between HBE cells and macrophages inhibited the IL-6/STAT3 pathway. M2 macrophage polarization was inhibited, and MMP9/12 release was reduced.Conclusion: Our results indicate that CS decreased let-7c expression in HBE cells, and M2 AM polarization was dominant in COPD. In HBE cells, let-7c could inhibit M2 polarization of AMs through the IL-6/STAT3 pathway, providing potential diagnostic and therapeutic value for slowing COPD emphysema.Keywords: let-7c, macrophage polarization, interleukin-6, IL-6/signal transducer and activator of transcription 3, STAT3, signaling pathway, emphysema, COPD
