Participation of miRNA-23a-3p in Pulmonary Tuberculosis Through Macrophages via the JAK-STAT Pathway

Background: This study investigated the role of miR-23a-3p in the pathogenesis of tuberculosis (TB)-associated obstructive pulmonary disease (TOPD) and its regulatory impact on THP-1 macrophages via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Methods: Patients with TOPD, TB patients without airflow obstruction (only TB), and healthy controls were recruited. Peripheral blood mononuclear cells were isolated, followed by RNA-seq analysis to identify differentially expressed microRNAs. Gene set enrichment analysis was used to identify enriched biological pathways. Additionally, enzyme-linked immunosorbent assays, Western blot, and flow cytometry were used to explore the miR-23a-3p-mediated modulation in macrophages (such as apoptosis and polarization) via the JAK-STAT pathway. Results: RNA-seq analysis identified miR-23a-3p as being significantly upregulated in TOPD patients. Bioinformatics analysis indicated that miR-23a-3p targets regulation of the JAK-STAT pathway. Overexpression of miR-23a-3p in macrophages led to decreased JAK1 protein expression and reduced levels of phosphorylated JAK1 and STAT1. Functional assays revealed that miR-23a-3p mitigates macrophage apoptosis and macrophage polarization as well as influences inflammatory cytokine production. Conclusion: miR-23a-3p regulates TOPD pathogenesis by modulating macrophage inflammation, apoptosis, and differentiation via the JAK-STAT pathway, making it a promising immunotherapeutic target for future treatments.