Macrophage migration inhibitory factor alleviates irradiation induced apoptosis of BMSCs through the LncRNA MEG3/NOX4 axis

Objectives: This study aimed to explore the mechanism by which exogenous macrophage migration inhibitory factor (MIF) reduces apoptosis of mouse bone marrow mesenchymal stem cells (BMSCs) induced by irradiation under high oxidative stress. Methods: BMSCs were cultured and exposed to irradiation using a linear accelerator to establish a radiation damage model. Cell viability was detected by the CCK-8 assay. Apoptosis rate and intracellular reactive oxygen species (ROS) production were measured by flow cytometry and fluorescence microscopy. The expression levels of Long non-coding RNA (lncRNA) MEG3, NOX4, and apoptosis-related genes were detected by western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunofluorescence. Results: The CCK-8 assay, western blot, and flow cytometry confirmed that irradiation effectively induced BMSCs apoptosis and upregulated the expression of lncRNA MEG3, which was positively correlated with NOX4 expression. Western blot, immunofluorescence, and RT-qPCR results demonstrated that MIF protected BMSCs from irradiation-induced apoptosis and downregulated the expression of MEG3 and NOX4. Furthermore, MEG3 siRNA was shown to reduce irradiation-induced apoptosis. Western blot and flow cytometry analyses revealed that overexpression of either NOX4 or MEG3 could reverse the protective effect of MIF. Conclusions: LncRNA MEG3 is an important regulatory factor in irradiation-induced apoptosis. The mechanism by which MIF protects BMSCs from irradiation-induced apoptosis is likely mediated through the regulation of the LncRNA MEG3/NOX4 signaling pathway.