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; Ruijie Liu

doi:10.1038/s41467-019-12433-w

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, Ruijie Liu

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103 Scopus citations

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.

Original language	English
Article number	4523
Journal	Nature Communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12433-w
State	Published - 1 Dec 2019

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title = "Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes",

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.",

author = "Yifei Zhong and Kyung Lee and Yueyi Deng and Yueming Ma and Yiping Chen and Xueling Li and Chengguo Wei and Shumin Yang and Tianming Wang and Wong, {Nicholas J.} and Muwonge, {Alecia N.} and Azeloglu, {Evren U.} and Weijia Zhang and Bhaskar Das and He, {John Cijiang} and Ruijie Liu",

note = "Publisher Copyright: {\textcopyright} 2019, This is a U.S. government work and not under copyright protection in the US; foreign copyright protection may apply.",

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doi = "10.1038/s41467-019-12433-w",

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T1 - Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes

AU - Zhong, Yifei

AU - Lee, Kyung

AU - Deng, Yueyi

AU - Ma, Yueming

AU - Chen, Yiping

AU - Li, Xueling

AU - Wei, Chengguo

AU - Yang, Shumin

AU - Wang, Tianming

AU - Wong, Nicholas J.

AU - Muwonge, Alecia N.

AU - Azeloglu, Evren U.

AU - Zhang, Weijia

AU - Das, Bhaskar

AU - He, John Cijiang

AU - Liu, Ruijie

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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

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