Methyltransferase 3-mediated m6A modification of Switch/sucrose non-fermenting-related matrix-associated actin-dependent regulator of chromatin subfamily a member 5 promotes mycobacterium tuberculosis-infected macrophage M1 polarization and inflammation
Year: 2025
Type: article
Abstract: Objective Mycobacterium tuberculosis (MTB) manipulates macrophage functions, thus mediating tuberculosis (TB) progression. Whether the switch/sucrose non-fermenting-related matrix-associated actin-dependent regulator of chromatin subfamily a member 5 (SMARCA5) mediates MTB-induced macrophage polarization remains unclear. Material and Methods Human Promyelocytic Leukemia Cell Line was induced into macrophages and then treated with MTB. Cell viability and apoptosis were tested with cell counting kit 8 assay and flow cytometry. Classically activated macrophages (M1) polarization and inflammation were measured by detecting CD86+ cell rate and inflammatory factor levels. The levels of SMARCA5, methyltransferase 3 (METTL3), and insulin-like growth factor 2 binding protein 1 (IGF2BP1) were assessed using quantitative real-time polymerase chain reaction or Western blot. The interaction between SMARCA5 and METTL3 or IGF2BP1 was confirmed by methylated RNA immunoprecipitation (RIP) and RIP assays. The effect of METTL3 knockdown on SMARCA5 messenger RNA (mRNA) stability was evaluated using actinomycin D treatment. Results MTB treatment suppressed the viability and promoted the apoptosis and M1 polarization and inflammation of macrophages (P < 0.05), and SMARCA5 knockdown abolished these effects (P < 0.05). METTL3 mediated the m6A methylation of SMARCA5 to enhance the mRNA stability of the latter, and this modification was recognized by IGF2BP1. SMARCA5 upregulation reverted the si-METTL3-mediated inhibition of MTB-induced macrophage M1 polarization and inflammation (P < 0.05). Conclusion METTL3-mediated SMARCA5 facilitates macrophage M1 polarization and inflammation, providing a novel target for TB treatment.
Source: CytoJournal
Authors: Cong Chen, Hai Huang
Institution: Wuhan Pulmonary Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4409030868