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MicroRNA-542-3p Regulates P-glycoprotein Expression in Rat Epilepsy via the Toll-like Receptor 4/Nuclear Factor-kappaB Signaling Pathway

[ Vol. 16 , Issue. 5 ]

Author(s):

YuKui Yan*, Hongping Xia, Jianqin Hu and Bing Zhang   Pages 433 - 440 ( 8 )

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.

Keywords:

miR-542-3p, TLR4, NF-κB, P-gp, epilepsy, hematoxylin-eosin.

Affiliation:

Department of Neurology, Huzhou Central Hospital, Huzhou City, Zhejiang Province, 313000, College of Basic Medicine, Nanjing Medical University, Nanjing City, Jiangsu Province, 211166, Department of Neurology, Huzhou Central Hospital, Huzhou City, Zhejiang Province, 313000, Department of Neurology, Huzhou Central Hospital, Huzhou City, Zhejiang Province, 313000



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