Bisphenol A-glycidyl methacrylate and triethylene glycol dimethacrylate cause reorganization of the actin cytoskeleton in human podocytes

AbstractBackgroundPodocyte integrity is critically dependent on the organization of the actin cytoskeleton, and disruption of cytoskeletal proteins is a key mechanism underlying glomerular barrier dysfunction. Dental resin–derived methacrylates, including triethylene glycol dimethacrylate (TEGDMA) and bisphenol A-glycidyl methacrylate (Bis-GMA), are known to exert cytotoxic effects in various cell types; however, their impact on podocyte cytoskeletal organization remains poorly understood.MethodsHuman podocytes were exposed to TEGDMA, Bis-GMA, or their combination at subtoxic concentrations. Spectrin protein expression was evaluated by Western blotting and densitometric analysis. Actin cytoskeletal organization was assessed by immunofluorescence microscopy using phalloidin staining to visualize filamentous actin. Proteomics and bioinformatics were performed to identify podocyte proteins differentially affected by TEGDMA or Bis-GMA treatment.ResultsWestern blot and densitometric analysis showed that the actin cytoskeleton protein spectrin is decreased more in human podocytes treated with TEG compared to BIS, and a combination of BIS and TEG treatment further decreases its protein expression. Immunofluorescence microscopy phalloidin staining for filamentous actin showed BIS and TEG caused a decrease in actin bundles and cytosketal networks in human podocytes. A proteomic analysis revealed several membrane and cytosolic proteins involved in signal transduction, transport, and cellular organization were differentially regulated at the protein level in these human podocytes treated with either monomer.ConclusionThese findings demonstrate that resin-derived methacrylates induce cytoskeletal injury in human podocytes by disrupting spectrin expression and actin organization. Such chemically induced alterations of the podocyte cytoskeleton may represent a previously underrecognized mechanism contributing to podocyte vulnerability and glomerular barrier dysfunction.