The Role And Mechanism Of LncRNA U90926 In Microglia Activation

BackgroundNeurodegenerative disease is a kind of chronic progressive injury of neurons,which is characterized by neuronal death,degeneration and necrosis.The related mechanism is not clear.Microglia(MG)is one of the glial cells in the brain.As important immune cells,microglia play a crucial role in the central nervous system,involved in various processes such as immune response,inflammatory response,and repair of nerve loss.When the brain is damaged or infected,microglia can differentiate into M1 microglia with neurotoxicity and M2 microglia with neuroprotective effect.M2 microglia can migrate to the site of loss for phagocytosis and necrosis,while M1 microglia can secrete inflammatory factors to damage surrounding neurons.LncRNA,as a kind of long non-coding RNA,inhibits the expression of target genes by regulating transcription and translation.As an epigenetic modifier,it is involved in a variety of biological processes and more and more diseases.At present,there are relatively few studies on the role of Lcn RNA U90926 in neurodegenerative diseases.Therefore,in this study,bacterial lipopolysaccharide was used to stimulate microglia to detect the expression of lncRNA U90926,and then to explore the effect of inhibiting lncRNA U90926 on LPS-induced oxidative stress and inflammatory response in primary microglia,and to analyze its mechanism,providing a new target for neurodegenerative diseases.ObjectiveTo investigate the effect of lncRNA U90926 on the phenotype and inflammatory response of microglia induced by lipopolysaccharide(LPS)and its mechanism.MethodPrimary microglia and BV2 cells(microglia cell line)were cultured in vitro.si RNA-Nrf2 and si RNA-U90926 were transfected into microglia according to Lipofectamine3000 kit,and negative control group was set up.LPS induced the activation of microglia to establish an inflammatory response model.The expression profile of lncRNA U90926 after LPS activation of microglia in vitro was detected by q RT-PCR.The m RNA expression levels of M1 markers i NOS,IL-1,IL-6 and TNF-αin microglia and the m RNA expression levels of M2 markers Arg1 and IL10 in microglia were also detected.The protein expression levels of TNF-α,IL-6,IL-1β,i NOS,Nrf2 and keap1 were determined by Western blot.ROS content was detected by flow cytometry.ResultsAfter LPS induced BV2 cells,the expression level of lncRNA U90926 was significantly up-regulated.At the same time,it also significantly enhanced its oxidative stress and inflammatory response,increased the expression of TNF-α,IL-6,IL-1β and ROS content.Therefore,after knocking down lncRNA U90926,the expression of M1-type markers i NOS m RNA,IL-1β,IL-6 and TNF-α was significantly reduced,and the expression of M2-type markers Arg-1 m RNA and IL-10 was significantly increased,and the ROS content was reduced to inhibit oxidative stress.Knockdown of lncRNA U90926 can target the activation of Nrf2 in BV2 cells and make it enter the nucleus to activate downstream pathways,thereby inhibiting the inflammatory response and oxidative stress of BV2 cells.ConclusionThe microglial cells of mice can be activated by bacterial lipopolysaccharide and transformed into M1 type,and the expression of lncRNA U90926 in the cells is significantly increased.Inhibition of lncRNA U90926 expression can hi nder the transformation of microglia to M1 type,and promote the transformatio n of microglia to M2 type through the Keap1/Nrf2-ARE signaling pathway,inh ibiting the inflammatory response and oxidative stress effect of microglia.This study suggests that lncRNA U90926 may be a key molecule in inhibiting neur oinflammation and a reliable strategy for preventing neurodegenerative diseases.