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  3. Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli

Egr-1 is a key regulator of the blood-brain barrier damage induced by meningitic Escherichia coli

  • Cell Commun Signal. 2024 Jan 17;22(1):44. doi: 10.1186/s12964-024-01488-y.
Ruicheng Yang 1 2,  Xinyi Wang 1 2,  Hulin Liu 1 2,  Jiaqi Chen 1 2,  Chen Tan 1 2 3 4,  Huanchun Chen 1 2 3 4,  Xiangru Wang 5 6 7 8
Affiliations

Affiliations

  • 1 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China.
  • 2 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
  • 3 Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, 430070, China.
  • 4 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, 430070, China.
  • 5 National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China. wangxr228@mail.hzau.edu.cn.
  • 6 Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China. wangxr228@mail.hzau.edu.cn.
  • 7 Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan, 430070, China. wangxr228@mail.hzau.edu.cn.
  • 8 International Research Center for Animal Disease, Ministry of Science and Technology of the People's Republic of China, Wuhan, 430070, China. wangxr228@mail.hzau.edu.cn.
PMID: 38233877 DOI: 10.1186/s12964-024-01488-y
Abstract

Bacterial meningitis remains a leading cause of infection-related mortality worldwide. Although Escherichia coli (E. coli) is the most common etiology of neonatal meningitis, the underlying mechanisms governing Bacterial blood-brain barrier (BBB) disruption during Infection remain elusive. We observed that Infection of human brain microvascular endothelial cells with meningitic E. coli triggers the activation of early growth response 1 (Egr-1), a host transcriptional activator. Through integrated chromatin immunoprecipitation Sequencing and transcriptome analysis, we identified Egr-1 as a crucial regulator for maintaining BBB integrity. Mechanistically, Egr-1 induced cytoskeletal changes and downregulated tight junction protein expression by directly targeting VEGFA, PDGFB, and ANGPTL4, resulting in increased BBB permeability. Meanwhile, Egr-1 also served as a master regulator in the initiation of neuroinflammatory response during meningitic E. coli Infection. Our findings support an Egr-1-dependent mechanism of BBB disruption by meningitic E. coli, highlighting a promising therapeutic target for Bacterial meningitis.

Keywords

Blood-brain barrier; Early growth response 1; Meningitic E. Coli; Neuroinflammation; Permeability.

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