Proteomic analysis of fibroblasts exposed to Bis-GMA

To investigate the dose-dependent effects of Bisphenol A-glycidyl methacrylate (Bis-GMA), a monomer released from dental resin composites, on the proteome of human gingival fibroblasts. Primary human gingival fibroblasts were exposed to different concentrations of Bis-GMA (0.002 mM, 0.02 mM, and 0.2 mM) for 72 h, and protein extracts were analyzed using two-dimensional electrophoresis coupled with liquid chromatography-tandem mass spectrometry. Differentially abundant proteins were identified and functionally classified using STRING and Gene Ontology enrichment analysis. A total of 45 proteins were differentially abundant across the three exposure conditions. At 0.002 mM, there were indicators of an adaptive response, with upregulation of proteins related to mitochondrial function and cytoskeletal integrity. At 0.02 mM, there were indicators of cellular stress, including alterations in nuclear transport, cytoskeletal disorganization, and energy metabolism. At 0.2 mM, there was a marked shift towards protein underabundance, which may indicate disruption of proteostasis, oxidative stress, and endoplasmic reticulum stress. The proteomic profiles reflect the progressive loss of homeostasis, culminating in a cellular state compatible with apoptosis or senescence. These findings raise concerns regarding low-level exposure to Bis-GMA, which is often encountered after dental restorations. These results support the necessity to adopt clinical procedures that minimize release of monomers and to develop safer monomers. • Bis-GMA exposure alters fibroblast proteome dose-dependently , impacting mitochondria , cytoskeleton organization, and stress pathways. • Low doses(0.002–0.02 mM), near clinical exposure , trigger stress that may progress to apoptosis or senescence. • Proteomic detects changes missed by cytotoxicity tests, supporting safer dental materials and stricter clinical protocols.