LncRNA H19 contributes to hippocampal glial cell activation via JAK/STAT signaling in a rat model of temporal lobe epilepsy

Abstract

BackgroundAstrocyte and microglia activation are well-known features of temporal lobe epilepsy that may contribute to epileptogenesis. However, the mechanisms underlying glia activation are not well understood. Long non-coding RNA (lncRNA) H19 has diverse functions depending on physiological or pathological state, and its role in epilepsy is unknown. We previously demonstrated that H19 was significantly upregulated in the latent period of epilepsy and may be associated with cell proliferation and immune and inflammatory responses. We therefore speculated that H19 is involved in the hippocampal glial cell activation during epileptogenesis.MethodsH19 was overexpressed or knocked down using an adeno-associated viral vector delivery system. A rat status epilepticus model was induced by intra-amygdala kainic acid injection. Astrocyte and microglia activation were assessed by immunofluorescence and western blot analyses. Expression of proinflammatory cytokines and components of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathways were evaluated with western blotting.ResultsH19 overexpression induced the activation of astrocytes and microglia and the release of proinflammatory cytokines (interleukin-1β and interleukin-6 and tumor necrosis factor-α) in the hippocampus, whereas H19 knockdown inhibited status epilepticus-induced glial cell activation. Moreover, H19 activated JAK/STAT signaling by promoting the expression of Stat3 and c-Myc, which is thought to be involved in astrocyte activation.ConclusionsLncRNA H19 contributes to hippocampal glial cell activation via modulation of the JAK/STAT pathway and could be a therapeutic tool to prevent the development of epilepsy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1139-z) contains supplementary material, which is available to authorized users.

Long noncoding RNA CASC9/miR‐519d/STAT3 positive feedback loop facilitate the glioma tumourigenesis

“…Interestingly, we found that STAT3 protein acted as the target of miR‐519d, constituting the CASC9‐miR‐519d‐STAT3 axis. STAT3 acts as a transcription factor . With the assistance of bioinformatic JASPAR tool, STAT3 could also bind with the promoter region of lncRNA CASC9, in turn, promoting the transcription activity of lncRNA CASC9.…”

“…STAT3 acts as a transcription factor. [26][27][28][29] With the assistance of bioinformatic JASPAR tool, STAT3 could also bind with the promoter region of lncRNA CASC9, in turn, promoting the transcription activity of lncRNA CASC9. Therefore, we conclude that CASC9 relieves the inhibition of STAT3 induced by miR-519d to recover STAT3 expression, reversely, STAT3 could activate the transcription activity of CASC9, forming the positive feedback loop of STAT3-CASC9-miR-519d-STAT3 axis.…”

Expression and functional analysis of lncRNAs in the hippocampus of immature rats with status epilepticus

“…20 Previous studies also have indicated that lncRNAs, H19 and UCA1, may be involved in the pathogenesis of SE via regulation of immune and inflammatory responses, cell apoptosis, activation of MAPK and NF-κB signalling pathway. [17][18][19] However, no study has been performed to investigate the expression profile of lncRNAs in SE.…”

“…16 In SE, H19-a lncRNA-was demonstrated to contribute to epileptogenesis by aggravating SE-induced neuronal loss, glial cell activation, mossy fibre sprouting and cognitive impairments in epileptic rats. 17 Whole-transcriptome screening revealed that H19 exhibited diverse functions related to epileptogenesis, including demyelination, immune and inflammatory responses, cell apoptosis and activation of MAPK. 18 UCA1, another lncRNA, may participate in the pathogenesis of epilepsy, which is evidenced by the dynamic change in the expressions of UCA1 and NF-κB during epilepsy.…”

LncRNA-UCA1 inhibits the astrocyte activation in the temporal lobe epilepsy via regulating JAK/STAT signaling pathway

“…Actually, the alternation of glial cells is strongly associated with the development of LTE [11] . A previous study shows that lncRNAs such as H19 promotes activation of hippocampal glial cells and serves as a therapeutic tool to prevent epileptogenesis by regulating JAK/STAT pathway [12] . The formation of glial fibrillary acidic protein (GFAP)-positive glia is realized by activation of JAK/STAT3 pathway [13] .…”