Down-Regulation of Annexin A Proteins in Human Mesangial Cells by TEGDMA and Bis-GMA Treatment Disrupts Proteins Involved in Cellular Function

Background: The cytotoxic effects of commonly used dental resin monomers, including bisphenol A-glycidyl methacrylate (Bis-GMA) and auxiliary monomers such as triethyleneglycol dimethacrylate (TEGDMA), have been studied in various cell types. However, their potential to affect kidney cells has not been investigated. Here, we hypothesized that both Bis-GMA and TEGDMA impair the function of human mesangial cells. Methods and Results: A proteomic approach revealed that multiple members of the annexin A family of proteins are differentially expressed in human mesangial cells treated with Bis-GMA or TEGDMA, compared to vehicle treatment. Western blotting and densitometric analysis further demonstrated downregulation of annexin A proteins, including annexin A2 and annexin A5, in human mesangial cells treated with TEGDMA. Transient knockdown of annexin A2 protein expression using annexin A2 siRNA resulted in a significant decrease in alpha smooth muscle actin and non-muscle myosin protein expression in human mesangial cells when compared to cells transfected with non-targeting control siRNA. Conclusions: Taken together, the results from this study suggest that commonly used dental monomers may adversely affect healthy human mesangial cells through a mechanism involving the downregulation of annexin A2 protein and the disruption of proteins essential for normal mesangial cell function.