Abstract WP347: Long Non-coding RNA TUG1 Contributes to Microglial Activation After Oxygen Glucose Deprivation

Abstract

Introduction: Microglial activation plays a critical role in inflammatory injury after ischemic stroke. Long non-coding RNA taurine up-regulated gene 1 (lncRNA TUG1) is widely expressed in adult brain and retina and has been reported to participate in multiple biological processes associated with nervous system diseases. However, the underlying function of TUG1 on inflammatory response and microglial activation after hypoxic insult remains unidentified. Methods: BV2 microglial cells were cultured in vitro and TUG1 siRNA was used to knockdown TUG1. Cells were subjected to oxygen-glucose deprivation (OGD) for 4 hours following TUG1 siRNA or scramble siRNA transient transfection. Then, the levels of TUG1 and inflammatory cytokines were assessed by quantitative real time PCR and ELISA. Microglial M1/M2 polarization was identified by western blot and immunofluorescence. Meanwhile, MiR-145a-5p was also detected to explore a potential interaction with TUG1. Results: OGD treatment led to downregulation of interleukin-10 and upregulation of tumor necrosis factor-α and interleukin-1β. The cellular level of TUG1 was significantly augmented while miR-145a-5p was significantly diminished in OGD-treated cells compared with normal control. By contrast, TUG1 knockdown increased the level of MiR-145a-5p, and further reversed OGD-induced changes of above inflammatory cytokines. Meanwhile, TUG1 knockdown blocked OGD-driven M1 microglial polarization, represented by decreased expression of CD68 (M1) and increased expression of Arg-1 (M2). Conclusion: Our study indicates that lncRNA TUG1, which could be as a miRNA sponge, is required for the release of inflammatory cytokines and microglial activation after OGD treatment, possibly providing a potential therapeutic target for inflammatory injury.