Long non-coding RNA Tug1 regulates inflammation in microglia and in status epilepticus rats through the NF-κB signaling pathway

Abstract

Abstract Background Inflammation plays an important role in the pathogenesis of status epilepticus (SE). The long non-coding RNA (lncRNA) taurine up-regulated gene1 (Tug1) plays a well-defined 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-1β and TNF-α was examined by real-time polymerase chain reaction (RT-PCR) and western blotting. Protein levels of p65, p-p65, p-ΙκΒα and ΙκΒα 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 of Tug1 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-ΙκΒα/ΙκΒα 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 significant role in the inflammatory processes, providing a valid target for the therapy of SE.