Macrophage-Secreted Exosomal HCG11 Promotes Autophagy in Antigen 85B-Infected Macrophages and Inhibits Fibroblast Fibrosis to Affect Tracheobronchial Tuberculosis Progression via the miR-601/Sirtuin 1 Axis

Abstract

Background: Tracheobronchial tuberculosis (TBTB) is a serious threat to human health. We aimed to explore the potential regulatory mechanism by which macrophages secrete exosomes that regulate TBTB progression. Methods: Bioinformatics analysis predicted lncRNAs with low expression in TBTB. Macrophage-derived exosomes were isolated and identified. HCG11 was knocked down and overexpressed, and miR-601 was overexpressed. ELISA was utilized to measure TGF-β, IL-8, IL-6 and IFN-γ levels. Based on bioinformatics prediction and dual-luciferase assay analysis, lncRNA HCG11 bound to miR-601, and miR-601 bound to SIRT1. The mRNA or protein expressions of lncRNA HCG11, miR- 601, SIRT1, PI3K/Akt/mTOR pathway-related factors, ATG5 and LC3B, as well as COL-1, MMP2, Timp-1 and Timp-3, were evaluated. Results: HCG11 was expressed at low levels in TBTB patients. Macrophage-secreted exosomes inhibited Ag85B-induced macrophage proinflammatory response and promoted autophagy. Moreover, normal macrophage (MØ)-exo-derived HCG11 could inhibit Ag85B-induced macrophage proinflammatory response and promote autophagy. HCG11 bound to miR-601, and miR-601 bound to SIRT1. HCG11 inhibited miR-601 to upregulate SIRT1. In addition, MØ-exo-derived HCG11 reduced Ag85B-induced fibroblast hyperproliferation and extracellular matrix deposition through the miR-601/SIRT1 axis. Conclusion: Macrophage-secreted exosomal HCG11 promotes autophagy in Ag85B-infected macrophages and inhibits fibroblast fibrosis to affect TBTB progression via the miR-601/SIRT1 axis.