Long non-coding RNA Tug 1 regulates inflammation in microglia and in status epilepticus rats through the NF-κB signaling pathway  

作　　者：Ming Wang Yangmei Xie Yiye Shao Yinghui Chen 

机构地区：[1]Department of Neurology,Huashan Hospital,Fudan University,Shang-hai 200040,China [2]Department of Neurology,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080,China.

出　　处：《Acta Epileptologica》2022年第2期88-96,共9页癫痫学报（英文）

基　　金：the Ethics Committee of Shanghai public clinical health center of Fudan University(No.2019JS015)。

摘　　要：Background:Inflammation plays an important role in the pathogenesis of status epilepticus(SE).The long non-cod-ing RNA(lncRNA)taurine up-regulated gene1(Tug1)plays a well-defned role in inflammatory diseases.However,the molecular mechanism of Tug1 in SE progression remains unknown.In present study,we investigated whether Tug1 is involved in microglial inflammation in SE rats.Methods:The SE rat model was established via intraperitoneal injection of lithium chloride pilocarpine.RNA-binding protein immunoprecipitation(RIP)and RIP sequencing were carried out in rat microglia(RM).Tug1 cloned into the adenovirus was overexpressed in the microglia.Knockdown of Tug1 was performed via siRNA transfection.The level of Tug1 and inflammatory factors IL-1βand TNF-αwas examined by real-time polymerase chain reaction(RT-PCR)and western blotting.Protein levels of p65,P-p65,p-IKBa and IkBa were assessed by western blotting.Results:The RIP-seq result showed 14 lncRNAs that bound to the NF-κB p65 protein in RM.The lncRNA Tug1 directly interacted with p65.The level of declined Tug1 was decreased in the hippocampus of SE rats.Overexpression ofTug1 reduced the LPS-induced inflammation and M1/M2 polarization of microglia,while knockdown of Tug1 aggravated the inflammatory response in microglia.Accordingly,the protein levels of p-p65/p65 and p-IkBa/IkBa were reduced in the Tug1-overexpression microglia and elevated in the Tug1-knockdown microglia.Conclusions:These findings indicate that Tug1 modulates the inflammation in microglia through the NF-κB signal pathway,and the Tug1/P65 axis are like to play a signifcant role in the inflammatory processes,providing a valid target for the therapy of SE.

关 键 词：INFLAMMATION MICROGLIA Status epilepticus lncRNA NF-κB signaling pathway Tug1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]