Circ_2858 helps blood-brain barrier disruption by increasing VEGFA via sponging miR-93-5p during Escherichia coli meningitis
发布时间 :2021-01-08
研究对象:Brain microvascular endothelial cells, circ_2858, miR-93-5p, V ascular endothelial growth factor A;期刊: Mol Ther Nucleic Acids;影响因子:7.032;合作单位:华中农业大学动物医学院 ;发表时间:2020年9月


摘要 

Meningitic Escherichia coli  invasion of the host brain can lead to increased blood-brain barrier (BBB) permeability. Circular RNAs (circRNAs) are non-coding RNAs, highly abundant in the brain that are widely involved in the pathological processes of central nervous system (CNS) disorders; however, whether circRNAs participate in the regulation of BBB permeability during E. coli  meningitis remains unknown. Here, we identified a novel circRNA, circ_2858, that was significantly upregulated in human brain microvascular endothelial cells (hBMECs) upon meningitic E. coli  infection. We also found that circ_2858 regulated BBB permeability in hBMECs by competitively binding miR-93-5p, thereby inducing the upregulation of vascular endothelial growth factor A and finally resulting in downregulation as well as altered distribution of tight junction proteins such as ZO-1, Occludin, and Claudin-5. These findings provide novel insights into the influence of circ_2858 on BBB permeability during the pathogenic process of E. coli  meningitis, suggesting potential nucleic acid targets for future prevention and therapy of CNS infection induced by meningitic E. coli .


Keywords:  Blood-brain barrier, Brain microvascular endothelial cells, circ_2858, miR-93-5p, V ascular endothelial growth factor A, Permeability


合作部分结果


伯信合作技术:circRNA FISH 探针、过表达载体

原文链接: DOI: 10.1016/j.omtn.2020.09.034