Improved Hepatic Regeneration With Reduced Injury by Redox Factor-1 in a Rat Small-Sized Liver Transplant Model

Authors

  • Lei Guo,

    1. Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Sanae Haga,

    1. Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan
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  • Shin Enosawa,

    1. Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan
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  • Katsutoshi Naruse,

    1. Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Yasushi Harihara,

    1. Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Yasuhiko Sugawara,

    1. Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Kaikobad Irani,

    1. Division of Cardiology, Department of Medicine, The John Hopkins University School of Medicine, Baltimore, MD, USA
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  • Masatoshi Makuuchi,

    1. Department of Artificial Organ and Transplantation Surgery, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Michitaka Ozaki

    Corresponding author
    1. Bioengineering Laboratory, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan
    2. Department of Food and Health Science, Okayama University Graduate School of Medicine and Dentistry, Faculty of Medicine, Okayama, Japan
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*Corresponding author: Michitaka Ozaki, mozaki@nch.go.jp

Abstract

Redox factor-1 (Ref-1) has been shown to function in a redox-dependent manner in the cell. This study was designed to examine the effects of Ref-1 on liver regeneration as well as protection against postischemic injury in a rat model of 20% partial liver transplantation. Adenovirus carrying the full length of Ref-1 gene was introduced into liver grafts by ex vivo perfusion via the portal vein during preservation. Liver graft weights were assessed, as well as graft histology, serum levels of alanine aminotransferase (ALT)/bilirubin, DNA binding activities of AP-1 and Stat3. Redox factor-1 successfully expressed in the liver graft, improved regeneration by promoting cell proliferation. Overexpression of Ref-1 protein also reduced post-transplant injury and inflammatory reactions in the grafts. The increased serum levels of ALT and bilirubin observed after transplantation were significantly reduced by Ref-1 overexpression. Furthermore, adenovirally overexpressed Ref-1 in mouse liver successfully promoted liver regeneration after simple partial hepatectomy. Interestingly, Ref-1 significantly increased DNA binding of Stat3, but not AP-1. Overexpressed Ref-1 effectively promoted graft regeneration and reduced postischemic injury in a small-sized liver transplantation model. The results of the present study may open a new avenue to clinical transplantation of disproportionately sized grafts in living-related liver transplantation.

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