Dataset Information

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

ABSTRACT: Arctigenin (ATG) is a major component of Fructus Arctii, which as a traditional herbal remedy reduced proteinuria in diabetic patients. However, whether ATG specifically provided renoprotection in DKD was 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 2A (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 its interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results clearly demonstrate a renoprotective mechanism of ATG via PP2A activation and establish PP2A as a potential target for DKD progression.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Early Embryonic Cell

SUBMITTER: Tong Liu

LAB HEAD: John Cijiang He

PROVIDER: PXD014976 | Pride | 2019-11-08

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	LiuRuijie_sample_ATG.mzid.gz	Mzid
	LiuRuijie_sample_ATG.mzid_LiuRuijie_sample_ATG.MGF	Mzid
	LiuRuijie_sample_ATG.mzid_LiuRuijie_sample_ATG.pride.mgf.gz	Mzid
	LiuRuijie_sample_ATG.pride.mztab.gz	Mztab
	LiuRuijie_sample_ATG.raw	Raw

Items per page:

1 - 5 of 35

Publications

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

Zhong Yifei Y Lee Kyung K Deng Yueyi Y Ma Yueming Y Chen Yiping Y Li Xueling X Wei Chengguo C Yang Shumin S Wang Tianming T Wong Nicholas J NJ Muwonge Alecia N AN Azeloglu Evren U EU Zhang Weijia W Das Bhaskar B He John Cijiang JC Liu Ruijie R

Nature communications 20191004 1

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 spectromet ...[more]

PMID: 31586053

Similar Datasets

Project description:Diabetic kidney disease, a major microvascular complication of diabetes, is the primary cause of end-stage renal disease globally 1. Current treatments mainly target glycemic, blood pressure, and lipid control but often fail to prevent renal impairment. Early DKD is characterized by tubular damage, glomerular hypertrophy, thickening of the glomerular basement membrane, and loss of podocytes. Podocyte damage and loss are potentially significant in the pathogenesis of DKD. Hyperglycemia, a critical factor in podocyte injury, can contribute to the progression of DKD. Therefore, mitigating podocyte injury may be a crucial factor in the future management and alleviation of DKD. Chronic hyperglycemia leads to podocyte dysfunction through inflammation, oxidative stress, autophagy, and apoptosis. As is well known, the non-enzymatic glycation of proteins, leading to the formation of advanced glycation end-products (AGEs), constitutes a significant contributing factor to DKD. Notably, recent studies underscore the crucial role of O-linked-N-acetylglucosamine (O-GlcNAc) modification (also known as O-GlcNAcylation) in DKD progression. The hexosamine biosynthesis pathway (HBP) converts glucose to UDP-N -acetylglucosamine (UDP-GlcNAc), a substrate for O-GlcNAcylation, which is catalyzed by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA). Aberrant O-GlcNAcylation is linked to renal fibrosis, inflammation, and apoptosis, which worsen diabetic kidney function. Elevated levels of O-GlcNAcylation have been observed in renal tissues of diabetic patients, indicating a potential link between hyperglycemia and dysregulated O-GlcNAc signaling. However, the exact molecular mechanisms of O-GlcNAcylation in DKD are not well understood. This study explores the changes in protein and glycosylated protein in podocytes after OGT knockdown to learn the molecular mechanisms of podocyte injury induced by high glucose (HG). A total of 128 up-regulated proteins and 45 down-regulated proteins in OGT knockdown group than in the control group were identified. Furthermore, 55 significantly changed glycosylation modification sites on 43 proteins were identified. To the best of our knowledge, this is the first study to conduct a global analysis of O-GlcNAcylation in podocytes.