Identification of MMP14 and FOS as Key Regulators of Vascular Smooth Muscle Cell Senescence in Diabetic Kidney Disease: A Combined Bioinformatics and Experimental Study

To investigate vascular smooth muscle cell (VSMC) senescence in diabetic kidney disease (DKD), this study integrated bioinformatics and machine learning to analyze DKD and VSMC aging transcriptomic datasets. Key genes MMP14 and FOS were identified through differential expression, WGCNA, and random forest analyses. They were significantly associated with cellular senescence and immune infiltration, demonstrating diagnostic value. Regulatory network analysis suggested potential ceRNA mechanisms and transcription factors. In a hyperglycemia-induced VSMC senescence model, experimental validation showed that overexpressing MMP14 or suppressing FOS promoted cell proliferation and alleviated senescence and apoptosis. This study identifies MMP14 and FOS as crucial regulators of VSMC senescence, providing new potential targets for DKD diagnosis and therapy.