<i>Magnolia kobus</i> DC. Regulates Vascular Smooth Muscle Cell Proliferation by Modulating <i>O</i>-GlcNAc and MOF Expression

Vascular smooth muscle cells (VSMCs) undergo metabolic pathway transitions, including aerobic glycolysis, fatty acid oxidation, and amino acid metabolism, which are important for their function. Metabolic dysfunction in VSMCs can lead to age-related vascular diseases. <i>O</i>-GlcNAcylation, a nutrient-dependent posttranslational modification linked specifically to glucose metabolism, plays an important role in this context. <i>Magnolia kobus</i> DC. (MK), derived from the flower buds of <i>Magnolia biondii</i>, is known for its anticancer, anti-allergy, and anti-inflammatory properties. However, the role of <i>O</i>-GlcNAcylation in VSMCs under aging and the association between MK and <i>O</i>-GlcNAc remain unclear. Therefore, the present study aimed to determine the effects of <i>O</i>-GlcNAc on VSMC proliferation, along with the expression of MOF (males absent on the first, KAT8) and its correlation with the efficacy of MK. The results showed that aging and <i>O</i>-GlcNAc induction increased the expression levels of <i>O</i>-GlcNAc, <i>O</i>-GlcNAc transferase (OGT), ataxia telangiectasia mutated (ATM) protein, and MOF in mouse vascular smooth muscle cells (MOVAS) and aorta tissue. Transfection with OGT siRNA reduced the expression of MOF and OGT, indicating that OGT regulates MOF and influences cell proliferation. MK treatment reduced the expression of OGT, ATM, and MOF, which was correlated with <i>O</i>-GlcNAc levels. These findings suggest that <i>O</i>-GlcNAcylation is important for VSMC homeostasis and may be a novel target for vascular diseases. Thus, MK exhibits potential as a new drug candidate for treating vascular diseases by modulating <i>O</i>-GlcNAcylation and MOF interactions.