@article{c82041605fc3450fa7b5ba56052aa3d2,
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 = "Funding Information: Y.Z. is supported by The 2018-2020 Three-year Action Plan for Traditional Chinese Medicine Further Development in Shanghai (ZY(2018-2020)-CCCX-2002-02); the National Natural Science Foundation of China (81573768); the Shanghai leadership program for Chinese Medicine (ZY(2018-2020)-RCPY-1007); the Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai (2017BR023); Shanghai Shuguang Scholar (16SG37); 2017 Xinglin training program for young talents in Shanghai University of Traditional Chinese Medicine-a follow up project; K.L. is supported by NIH 1R01DK117913; E.U.A. is supported by NIH 1R01DK118222; J.C.H. is supported by NIH 1R01DK078897, NIH 1R01DK088541, and VA Merit Award. The mass spectrometry data were obtained from an Orbitrap mass spectrometer funded in part by an NIH grant NS046593 and 1S10OD025047-01 for the support of the Rutgers Mass Spectrometry Center for Integrative Neuroscience Research. Publisher Copyright: {\textcopyright} 2019, This is a U.S. government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2019",
month = dec,
day = "1",
doi = "10.1038/s41467-019-12433-w",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}