Tumor necrosis factor receptor-associated factor 5 is an essential mediator of ischemic brain infarction

Authors

  • Lang Wang,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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    • Lang Wang and Yanyun Lu contributed equally to this work.
  • Yanyun Lu,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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    • Lang Wang and Yanyun Lu contributed equally to this work.
  • Hongjing Guan,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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  • Dingsheng Jiang,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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  • Yu Guan,

    1. Department of Thoracic and Cardiovascular Surgery, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, PR China
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  • Xin Zhang,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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  • Hiroyasu Nakano,

    1. Department of Immunology, Juntendo University Graduate School of Medicine, Tokyo, Japan
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  • Yan Zhou,

    1. College of Life Sciences, Wuhan University, Wuhan, PR China
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  • Yan Zhang,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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  • Li Yang,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
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  • Hongliang Li

    Corresponding author
    1. Cardiovascular Research Institute of Wuhan University, Wuhan, PR China
    • Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, PR China
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Address correspondence and reprint requests to Hongliang Li, MD, PhD, Professor and Director, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan 430060, PR China. E-mail: lihl@whu.edu.cn

Abstract

Tumor necrosis factor receptor-associated factor 5 (TRAF5) is an adaptor protein of the tumor necrosis factor (TNF) receptor superfamily and the interleukin-1 receptor/Toll-like receptor superfamily and plays important roles in regulating multiple signaling pathways. This study was conducted to investigate the role of TRAF5 in the context of brain ischemia/reperfusion (I/R) injury. Transient occlusion of the middle cerebral artery was performed on TRAF5 knockout mice (KO), neuron-specific TRAF5 transgene (TG), and the appropriate controls. Compared with the WT mice, the TRAF5 KO mice showed lower infarct volumes and better outcomes in the neurological tests. A low neuronal apoptosis level, an attenuated blood-brain barrier (BBB) disruption and an inhibited inflammatory response were exhibited in TRAF5 KO mice. TRAF5 TG mice exhibited an opposite phenotype. Moreover, the Akt/FoxO1 signaling pathway was enhanced in the ischemic brains of the TRAF5 KO mice. These results provide the first demonstration that TRAF5 is a critical mediator of I/R injury in an experimental stroke model. The Akt /FoxO1 signaling pathway probably plays an important role in the biological function of TRAF5 in this model.

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