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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Nat Commun. 2019 10 4 ;10(1):4523. Epub 2019 Oct 4. PMID: 31586053

Abstract Author(s):

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

Article Affiliation:

Yifei Zhong

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 PP2Aactivation and establish PP2A as a potential target for DKD progression.

Study Type : Animal Study

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