Title:MicroRNA-542-3p Regulates P-glycoprotein Expression in Rat Epilepsy via the Toll-like Receptor 4/Nuclear Factor-kappaB Signaling Pathway
Volume: 16
Issue: 5
Author(s): YuKui Yan*, Hongping Xia, Jianqin Hu and Bing Zhang
Affiliation:
- Department of Neurology, Huzhou Central Hospital, Huzhou City, Zhejiang Province, 313000,China
Keywords:
miR-542-3p, TLR4, NF-κB, P-gp, epilepsy, hematoxylin-eosin.
Abstract:
Background: The function of microRNA-542-3p (miR-542-3p) in rat epilepsy is still
unclear.
Methods: The levels of miR-542-3p and toll-like receptor 4 (TLR4) were determined through
quantitative real-time PCR. The protein levels were examined via the western blot analysis. The
relationship between miR-542-3p and TLR4 was confirmed through luciferase assay. Pathological
changes were analyzed via Hematoxylin-eosin (HE) and Nissl staining.
Results: The rats and hippocampal cells were treated with kainic acid (KA) in vivo and in vitro.
miR-542-3p was low in KA-treated rats, hippocampal cells and cerebrospinal fluid of patients with
epilepsy. Further functional analysis showed that miR-542-3p overexpression inhibited KAinduced
average seizure frequency, damage of hippocampal neuron and cell apoptosis, leading to
the alleviation of the brain injury in epilepsy rats. miR-542-3p was determined to downregulate
TLR4 expression. The relationship between miR-542-3p and TLR4 was confirmed. TLR4 knockdown
reduced KA-induced nuclear factor-kappa B p65 (NF-κB p65), multidrug resistance 1
(MDR1), P-glycoprotein (P-gp) and apoptosis-associated protein levels. Further, for NF-κB p65,
MDR1, P-gp and apoptosis-associated protein levels detection, miR-542-3p mimic showed a suppressive
effect on these KA-induced protein levels, whereas TLR4 overexpression ameliorated the
miR-542-3p-induced these protein levels in KA-treated epilepsy rats.
Conclusion: We identified that miR-542-3p attenuated seizure-induced brain injury and the expression
of P-gp in epilepsy rats through inhibiting TLR4/NF-κB signaling pathway, which might
contribute to improved epilepsy therapy.
