Exosomal miR-203 from bone marrow stem cells targets the SOCS3/NF-κB pathway to regulate neuroinflammation in temporal lobe epilepsy  

作　　者：Wei Wang Jian Yin 

机构地区：[1]Department of Neurosurgery,The Second Affiliated Hospital of Dalian Medical University,Dalian 116023,Liaoning Province,China

出　　处：《World Journal of Stem Cells》2025年第2期105-123,共19页世界干细胞杂志(英文)

摘　　要：BACKGROUND Epilepsy is a prevalent chronic neurological disorder affecting 50 million individuals globally,with temporal lobe epilepsy(TLE)being the most common form.Despite advances in antiepileptic drug development,over 30%of patients suffer from drug-resistant epilepsy,which can lead to severe cognitive impairments and adverse psychosocial outcomes.AIM To explore the role of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-203 in the regulation of neuroinflammation in a mouse model of epilepsy,providing a theoretical basis for the development of targeted microRNA delivery therapies for drug-resistant epilepsy.METHODS Adult male C57BL/6 mice were divided into a control group and a TLE model of 30 mice each,and the TLE model group was established by injecting kainic acid.BMSCs were isolated from the mice,and exosomes were purified using ultracentrifugation.Exosomal miR-203 was identified and characterized using highthroughput sequencing and quantitative reverse-transcription polymerase chain reaction.The uptake of exosomes by hippocampal neurons and the subsequent effects on neuroinflammatory markers were assessed using in vitro cell culture models.RESULTS Exosomal miR-203 exhibited a significant upregulation in BMSCs derived from epileptic mice.In vitro investigations demonstrated the efficient internalization of these exosomes by hippocampal neurons,resulting in downregulation of suppressor of cytokine signaling 3 expression and activation of the nuclear factor kappaB pathway,ultimately leading to enhanced secretion of pro-inflammatory cytokines.CONCLUSION Our study identifies exosomal miR-203 as a key regulator of neuroinflammation in a mouse model of epilepsy.The findings suggest that targeting miR-203 may offer a novel therapeutic strategy for epilepsy by modulating the suppression of cytokine signaling 3/nuclear factor kappaB pathway,thus providing a potential avenue for the development of cell-free therapeutics.

关 键 词：EPILEPSY NEUROINFLAMMATION MiR-203 EXOSOMES Bone marrow mesenchymal stem cells Suppressor of cytokine signaling Nuclear factor kappaB 

分 类 号：R743.3[医药卫生—神经病学与精神病学]