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Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes

Author

Listed:
  • Yifei Zhong

    (Shanghai University of Traditional Chinese Medicine)

  • Kyung Lee

    (Icahn School of Medicine at Mount Sinai)

  • Yueyi Deng

    (Shanghai University of Traditional Chinese Medicine)

  • Yueming Ma

    (Shanghai University of Traditional Chinese Medicine)

  • Yiping Chen

    (Shanghai University of Traditional Chinese Medicine)

  • Xueling Li

    (Shanghai University of Traditional Chinese Medicine)

  • Chengguo Wei

    (Icahn School of Medicine at Mount Sinai)

  • Shumin Yang

    (Icahn School of Medicine at Mount Sinai)

  • Tianming Wang

    (Shanghai University of Traditional Chinese Medicine)

  • Nicholas J. Wong

    (Icahn School of Medicine at Mount Sinai)

  • Alecia N. Muwonge

    (Icahn School of Medicine at Mount Sinai)

  • Evren U. Azeloglu

    (Icahn School of Medicine at Mount Sinai)

  • Weijia Zhang

    (Icahn School of Medicine at Mount Sinai)

  • Bhaskar Das

    (Icahn School of Medicine at Mount Sinai)

  • John Cijiang He

    (Icahn School of Medicine at Mount Sinai
    James J Peters Veterans Affair Medical Center)

  • Ruijie Liu

    (Icahn School of Medicine at Mount Sinai)

Abstract

Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.

Suggested Citation

  • Yifei Zhong & Kyung Lee & Yueyi Deng & Yueming Ma & Yiping Chen & Xueling Li & Chengguo Wei & Shumin Yang & Tianming Wang & Nicholas J. Wong & Alecia N. Muwonge & Evren U. Azeloglu & Weijia Zhang & Bh, 2019. "Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12433-w
    DOI: 10.1038/s41467-019-12433-w
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    Cited by:

    1. Ying Zhao & Shijie Fan & Hong Zhu & Qingqing Zhao & Zimin Fang & Diyun Xu & Wante Lin & Liming Lin & Xiang Hu & Gaojun Wu & Julian Min & Guang Liang, 2024. "Podocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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