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

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, Bhaskar Das, John Cijiang He () and Ruijie Liu
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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
Ruijie Liu: Icahn School of Medicine at Mount Sinai

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12433-w

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