摘要
星形胶质细胞是大脑炎症过程的重要介质,可能在包括癫痫在内的几种神经系统疾病中起重要作用。星形胶质细胞中可生产几种miRNA,是炎症通路的关键调节因子,还可能用作治疗靶标。本研究将探索在体外IL-1β介导的炎症条件下,星形胶质细胞内生成的miRNA及其功能,并在人癫痫脑组织中验证。我们通过测序评估IL-1β刺激的人胎儿星形胶质细胞培养物中的miRNA和mRNA表达。使用miRNA模拟物在细胞培养物中过表达miRNA。使用原位杂交技术检测患有结节性硬化症复合体或颞叶癫痫伴海马硬化患者的切除脑组织中miRNA的表达。我们发现了2种差异表达的miRNA:miR146a和miR147b,它们与免疫/炎症反应相关基因的表达增加有关。既往有研究报道,在星形胶质细胞和结节性硬化复合细胞培养物中使用IL-1β刺激后,miR147b的过表达降低了促炎介质IL-6和COX-2的表达。miR146a和miR147b过表达降低了星形胶质细胞的增殖并促进人神经干细胞的神经元分化。miR147b在致癫痫脑中的星形胶质细胞中表达增加。由于其抗炎和恢复异常星形细胞增殖和促进神经元分化的能力,miR146a和miR147b作为与炎症相关的神经疾病(例如癫痫)的潜在治疗靶标值得进一步研究。
Astrocytes are important mediators of inflammatory processes in the brain and seem to play an important role in several neurological disorders,including epilepsy.Recent studies show that astrocytes produce several microRNAs,which may function as crucial regulators of inflammatory pathways and could be used as therapeutic target.We aim to study which miRNAs are produced by astrocytes during IL-1βmediated inflammatory conditions in vitro,as well as their functional role and to validate these findings in human epileptogenic brain tissue.Sequencing was used to assess miRNA and mRNA expression in IL-1β-stimulated human fetal astrocyte cultures.miRNAs were overexpressed in cell cultures using miRNA mimics.Expression of miRNAs in resected brain tissue from patients with tuberous sclerosis complex or temporal lobe epilepsy with hippocampal sclerosis was examined using in situ hybridization.Two differentially expressed miRNAs were found:miR146a and miR147b,which were associated with increased expression of genes related to the immune/inflammatory response.As previously reported for miR146a,overexpression of miR147b reduced the expression of the pro-inflammatory mediators IL-6 and COX-2 after IL-1βstimulation in both astrocyte and tuberous sclerosis complex cell cultures.miR146a and miR147b overexpression decreased proliferation of astrocytes and promoted neuronal differentiation of human neural stem cells.Similarly to previous evidence for miR146a,miR147b was increased expressed in astrocytes in epileptogenic brain.Due to their anti-inflammatory effects,ability to restore aberrant astrocytic proliferation and promote neuronal differentiation,miR146a and miR147b deserve further investigation as potential therapeutic targets in neurological disorders associated with inflammation,such as epilepsy.
出处
《神经损伤与功能重建》
2018年第12期662-662,共1页
Neural Injury and Functional Reconstruction
