Down-regulated microRNA-183 mediates the Jak/Stat signaling pathway to attenuate hippocampal neuron injury in epilepsy rats by targeting Foxp1

下调的microRNA-183通过靶向Foxp1介导Jak/Stat信号通路,从而减轻癫痫大鼠海马神经元损伤。

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Abstract

Recently, the impacts of microRNAs (miRNAs) have been identified in epilepsy (EP), this study was designed to assess the role of miR-183 in hippocampal neuron injury in EP. Rat EP models were established by injected with lithium-pilocarpine. The pathological observation of rats' hippocampus sections was conducted. Expression of miR-183, Foxp1, Jak1, Stat1, and Stat3 in rats' hippocampal tissues was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The proliferation ability and the apoptosis of the rats' neurons were measured. Furthermore, the target relation between miR-183 and Foxp1 was determined by bioinformatics analysis and dual-luciferase gene reporter assay. The levels of miR-183, Jak1, Stat1, and Stat3 were elevated, and the expression of Foxp1 was declined in EP rats' hippocampal tissues. Inhibited miR-183 could up-regulate Foxp1, inhibited miR-183 together with up-regulated Foxp1 could repress hippocampal neuron injury, promote neuron proliferation, suppress neuron apoptosis, and inactivate the Jak/Stat signaling pathway, resulting in an attenuation of EP progression. Moreover, down-regulated Foxp1 could reverse the attenuation of EP progression which was contributed by inhibited miR-183. Our study implies that inhibited miR-183 could up-regulate Foxp1, resulting in an inactivation of the Jak/Stat signaling pathway and promotion of neuron proliferation, as well as inhibition of apoptosis of hippocampal neurons in EP rats, by which the hippocampal neuron injury and EP progression could be repressed.

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