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Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes.
- Source :
-
Nature communications [Nat Commun] 2019 Oct 04; Vol. 10 (1), pp. 4523. Date of Electronic Publication: 2019 Oct 04. - Publication Year :
- 2019
-
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.
- Subjects :
- Animals
Arctium chemistry
Diabetes Mellitus, Experimental chemically induced
Diabetic Nephropathies etiology
Diabetic Nephropathies pathology
Disease Progression
Furans therapeutic use
Humans
Lignans therapeutic use
Male
Mice
Mice, Knockout
Microscopy, Electron, Transmission
Nitric Oxide Synthase Type III genetics
Podocytes pathology
Podocytes ultrastructure
Protein Phosphatase 2 genetics
Streptozocin toxicity
Treatment Outcome
Diabetes Mellitus, Experimental complications
Diabetic Nephropathies drug therapy
Furans pharmacology
Lignans pharmacology
Podocytes drug effects
Protein Phosphatase 2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31586053
- Full Text :
- https://doi.org/10.1038/s41467-019-12433-w