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Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury

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  • Mariko Hara-Chikuma

    (Keio University)

  • Manami Tanaka

    (Keio University
    Keio Global Research Institute, Center for Water Biology and Medicine)

  • Alan S. Verkman

    (University of California San Francisco)

  • Masato Yasui

    (Keio University
    Keio Global Research Institute, Center for Water Biology and Medicine)

Abstract

Aquaporin 3 (AQP3) is a transporter of water, glycerol and hydrogen peroxide (H2O2) that is expressed in various epithelial cells and in macrophages. Here, we developed an anti-AQP3 monoclonal antibody (mAb) that inhibited AQP3-facilitated H2O2 and glycerol transport, and prevented liver injury in experimental animal models. Using AQP3 knockout mice in a model of liver injury and fibrosis produced by CCl4, we obtained evidence for involvement of AQP3 expression in nuclear factor-κB (NF-κB) cell signaling, hepatic oxidative stress and inflammation in macrophages during liver injury. The activated macrophages caused stellate cell activation, leading to liver injury, by a mechanism involving AQP3-mediated H2O2 transport. Administration of an anti-AQP3 mAb, which targeted an extracellular epitope on AQP3, prevented liver injury by inhibition of AQP3-mediated H2O2 transport and macrophage activation. These findings implicate the involvement of macrophage AQP3 in liver injury, and provide evidence for mAb inhibition of AQP3-mediated H2O2 transport as therapy for macrophage-dependent liver injury.

Suggested Citation

  • Mariko Hara-Chikuma & Manami Tanaka & Alan S. Verkman & Masato Yasui, 2020. "Inhibition of aquaporin-3 in macrophages by a monoclonal antibody as potential therapy for liver injury," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19491-5
    DOI: 10.1038/s41467-020-19491-5
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