1. Academic Validation
  2. circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Escherichia coli Meningitis

circ_2858 Helps Blood-Brain Barrier Disruption by Increasing VEGFA via Sponging miR-93-5p during Escherichia coli Meningitis

  • Mol Ther Nucleic Acids. 2020 Oct 4;22:708-721. doi: 10.1016/j.omtn.2020.09.034.
Ruicheng Yang 1 2 Jiaqi Chen 1 2 Bojie Xu 1 2 Bo Yang 1 2 Jiyang Fu 1 2 Siyu Xiao 1 2 Chen Tan 1 2 3 4 Huanchun Chen 1 2 3 4 Xiangru Wang 1 2 3 4
Affiliations

Affiliations

  • 1 The Cooperative Innovation Center for Sustainable Pig Production, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 2 State Key Laboratory of Agricultural Microbiology, Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei 430070, China.
  • 3 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, Wuhan, Hubei, China.
  • 4 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, Hubei, China.
Abstract

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; permeability; vascular endothelial growth factor A.

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