2. Academic Validation
  3. Enterovirus 71 infection induced Aquaporin-4 depolarization by increasing matrix metalloproteinase-9 activity

Enterovirus 71 infection induced Aquaporin-4 depolarization by increasing matrix metalloproteinase-9 activity

  • Neurosci Lett. 2021 Aug 10;759:136049. doi: 10.1016/j.neulet.2021.136049.
Huanru Wang 1,  Meng Yuan 2,  Enhui Yang 3,  Deyan Chen 2,  Airong Su 4,  Zhiwei Wu 5
Affiliations

Affiliations

  • 1 Center for Public Health Research, Medical School, Nanjing University, Nanjing, China; Microbiology Laboratory, Shanghai Municipal Centre for Disease Control and Prevention, Shanghai, China.
  • 2 Center for Public Health Research, Medical School, Nanjing University, Nanjing, China.
  • 3 Children's Hospital of Nanjing Medical University, Nanjing, China.
  • 4 Clinical Molecular Diagnostic Laboratory, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 5 Center for Public Health Research, Medical School, Nanjing University, Nanjing, China; State Key Lab of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China. Electronic address: wzhw@nju.edu.cn.
PMID: 34126180 DOI: 10.1016/j.neulet.2021.136049
Abstract

Aquaporin-4 (AQP4) is the key water channel protein that regulates brain water homeostasis. Polarized expression of AQP4 on the astroglial endfeet facilitates its role in bi-directional brain water flux control. In the current study, we found that Enterovirus 71 (EV71) Infection induced depolarization of AQP4 in mouse brain, and demonstrated that β-dystroglycan (β-DG), the key component of dystrophin glycoprotein complex (DGC) that anchors AQP4 to the astroglial endfeet, was degraded upon Infection. Elevated activity or expression of matrix metalloproteinase 9 (MMP9) upon Infection was found in both mouse brains and patient cerebrospinal fluid (CSF) samples. Inhibiting MMP9 activity by SB-3CT rescued the decay of β-DG and reduced the depolarization of AQP4. Brain edema induced by viral Infection was also ameliorated by SB-3CT treatment in mice.

Keywords

Aquaporin-4; Astrocytes; Enterovirus 71; Matrix metalloproteinase; β-dystroglycan.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12354
    99.59%, MMP2/9 Inhibitor
    MMP