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.