The lncRNA H19 binding to let‐7b promotes hippocampal glial cell activation and epileptic seizures by targeting Stat3 in a rat model of temporal lobe epilepsy

• Published in: Cell proliferation Vol. 53; no. 8; pp. e12856 - n/a
• Main Authors: Han, Chun‐Lei, Liu, Yun‐Peng, Guo, Chen‐Jia, Du, Ting‐Ting, Jiang, Ying, Wang, Kai‐Liang, Shao, Xiao‐Qiu, Meng, Fan‐Gang, Zhang, Jian‐Guo
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Inc 01.08.2020; John Wiley and Sons Inc
• Subjects: Alzheimer's disease; astrocytes; Binding; Brain damage; Cell activation; Convulsions & seizures; Cytoplasm; Environmental monitoring; Epilepsy; Fluorescence; Fluorescence in situ hybridization; Gene expression; Glial cells; Hippocampus; Hybridization; Hypoxia; Inflammation; inflammatory; Inflammatory response; Kainic acid; lncRNA; microglia; microRNA; Mossy fibers; Non-coding RNA; Original; Ribonucleic acid; RNA; Seizures; Software; Stat3 protein; Studies; Temporal lobe; temporal lobe epilepsy; Variance analysis
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12856

Objectives Glial cell activation contributes to the inflammatory response and occurrence of epilepsy. Our preliminary study demonstrated that the long non‐coding RNA, H19, promotes hippocampal glial cell activation during epileptogenesis. However, the precise mechanisms underlying this effect remain unclear. Materials and methods H19 and let‐7b were overexpressed or silenced using an adeno‐associated viral vector in vivo. Their expression in a kainic acid‐induced epilepsy model was evaluated by real‐time quantitative PCR, fluorescence in situ hybridization, and cytoplasmic and nuclear RNA isolation. A dual‐luciferase reporter assay was used to evaluate the direct binding of let‐7b to its target genes and H19. Western blot, video camera monitoring and Morris water maze were performed to confirm the role of H19 and let7b on epileptogenesis. Results H19 was increased in rat hippocampus neurons after status epilepticus, which might be due to epileptic seizure‐induced hypoxia. Increased H19 aggravated the epileptic seizures, memory impairment and mossy fibre sprouting of the epileptic rats. H19 could competitively bind to let‐7b to suppress its expression. Overexpression of let‐7b inhibited hippocampal glial cell activation, inflammatory response and epileptic seizures by targeting Stat3. Moreover, overexpressed H19 reversed the inhibitory effect of let‐7b on glial cell activation. Conclusions LncRNA H19 could competitively bind to let‐7b to promote hippocampal glial cell activation and epileptic seizures by targeting Stat3 in a rat model of temporal lobe epilepsy.