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목적 : Nuclear factor-Kappa B (NF-κB) is considered to have associated with the epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPE). We investigated the effects of proteasome inhibitor, bortezomib, on EMT of RPE cells by regulating NF-κB pathway.
방법 : After applying a bortezomib, the cell cycle regulations were evaluated by the flow cytometry in RPE cells. The cell migration was investigated by wound healing as well as transwell migration assay. In this vein, recombinant human TGF-β1 (10ng/mL) was applied to RPE cell to induce EMT, and western blot and immunocytochemical analyses were performed to evaluate the altered expressions of EMT markers after the treatments of bortezomib.
결과 : Bortezomib treatments showed dose-dependent decrement of RPE cell viability and we confirmed that these effects were induced by G2/M phase cell cycle arrest with the flow cytometry. The application of 20nM bortezomib significantly impeded RPE cell migration in an in vitro wound healing and transwell migration assay. Bortezomib treatments significantly inhibited TGF-β1 induced EMT of RPE. In this regard, we finally confirmed that these EMT regulations were arisen by the regulation of NF-κB signaling pathway.
결론 : Our study showed that bortezomib successfully inhibits EMT of RPE cells by regulation of NF-κB expressions. Bortezomib treatments also induce G2/M phase arrest and decreased the level of cell viability. Therefore, Bortezomib treatments may suggest a clue for the treatment, and in turn a prevention of EMT related retinal pathologies.
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