Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier
| Autor: | Jiyang Fu, Wen-Tong Liu, Chen Tan, Xiangru Wang, Xin Zong, Beibei Dou, Ruicheng Yang, Ling Miao, Huanchun Chen, Aoling Cai, Xiaopei Yang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine Chemokine tight junctions Biology Blood–brain barrier medicine.disease_cause Permeability Microbiology Proinflammatory cytokine Snail-1 Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Escherichia Escherichia coli medicine Animals Humans Meningitis Escherichia coli Infections Inflammation Tight Junction Proteins Tight junction blood-brain barrier biology.organism_classification Up-Regulation Disease Models Animal Vascular endothelial growth factor A 030104 developmental biology medicine.anatomical_structure Oncology Immunology biology.protein Cytokines Snail Family Transcription Factors bacterial meningitis 030217 neurology & neurosurgery Research Paper Signal Transduction |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ruicheng Yang 1, 2 , Wentong Liu 1, 2 , Ling Miao 1, 2 , Xiaopei Yang 1, 2 , Jiyang Fu 1, 2 , Beibei Dou 1, 2 , Aoling Cai 1, 2 , Xin Zong 1, 2 , Chen Tan 1, 2, 3 , Huanchun Chen 1, 2, 3 , Xiangru Wang 1, 2, 3 1 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei 430070, China 2 The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, Hubei 430070, China 3 Key Laboratory of development of veterinary diagnostic products of Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei 430070, China Correspondence to: Xiangru Wang, email: wangxr228@mail.hzau.edu.cn Keywords: blood-brain barrier, tight junctions, vascular endothelial growth factor A, Snail-1, bacterial meningitis Received: April 12, 2016 Accepted: August 24, 2016 Published: August 30, 2016 ABSTRACT Escherichia coli is the most common Gram-negative bacterium that possesses the ability to cause neonatal meningitis, which develops as circulating bacteria penetrate the blood-brain barrier (BBB). However, whether meningitic E. coli could induce disruption of the BBB and the underlying mechanisms are poorly understood. Our current work highlight for the first time the participation of VEGFA and Snail-1, as well as the potential mechanisms, in meningitic E. coli induced disruption of the BBB. Here, we characterized a meningitis-causing E. coli PCN033, and demonstrated that PCN033 invasion could increase the BBB permeability through downregulating and remodeling the tight junction proteins (TJ proteins). This process required the PCN033 infection-induced upregulation of VEGFA and Snail-1, which involves the activation of TLR2-MAPK-ERK1/2 signaling cascade. Moreover, production of proinflammatory cytokines and chemokines in response to infection also promoted the upregulation of VEGFA and Snail-1, therefore further mediating the BBB disruption. Our observations reported here directly support the involvement of VEGFA and Snail-1 in meningitic E. coli induced BBB disruption, and VEGFA and Snail-1 would therefore represent the essential host targets for future prevention of clinical E. coli meningitis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|