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Astragaloside IV represses high glucose-induced mesangial cells activation by enhancing autophagy via SIRT1 deacetylation of NF-κB P65 subunit

Authors Wang X, Gao Y, Tian N, Zhu Z, Wang T, Xu J, Wu B, Zhang N

Received 30 May 2018

Accepted for publication 2 August 2018

Published 12 September 2018 Volume 2018:12 Pages 2971—2980

DOI https://doi.org/10.2147/DDDT.S174058

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sukesh Voruganti


Xiaolei Wang,1,2 Yanbin Gao,1,2 Nianxiu Tian,1 Zhiyao Zhu,2 Tao Wang,1 Jiayi Xu,1 Bingjie Wu,1 Nan Zhang2

1Department of Endocrinology, School of Traditional Chinese Medicine, Capital Medical University, Beijing, China; 2Department of Endocrinology, Beijing Key Lab of Traditional Chinese Medicine Collateral Disease theory Research, Capital Medical University, Beijing, China

Aim: Mesangial cell (MC) activation plays an important role in many glomerular diseases associated with renal fibrosis, including diabetic kidney disease (DKD). The aim of this study was to determine whether Astragaloside IV (AS-IV) modulated MC activation in DKD via autophagy by specifically regulating the autophagy inducer sirtuin 1 (SIRT1).
Methods: Cultured MCs and diabetic KK-Ay mice were treated with AS-IV, and the markers and regulatory mediators of autophagy were analyzed using Western blotting, real-time PCR, ELISA and IF.
Results: AS-IV inhibited MC activation and enhanced autophagy in hyperglycemic conditions by increasing SIRT1 expression and decreasing NF-κB p65 acetylation. In addition, the SIRT1 activator SRT1720 enhanced autophagy and decreased p65 acetylation during hyperglycemia-induced MC activation. Opposite effects were seen with the SIRT1 inhibitor EX527. Furthermore, the ameliorative effect of AS-IV on MCs was abolished by the autophagy inhibitor 3-MA, while the autophagy activator rapamycin restored hyperglycemia-induced MC activation. Finally, AS-IV improved renal function and fibrosis in the diabetic KK-Ay mice.
Conclusion: AS-IV ameliorated renal function and morphology by inducing autophagy and inhibiting MC activation through the SIRT1-NF-κB pathway, indicating a potential therapeutic role of AS-IV in glomerular diseases.

Keywords: Chinese medicine, pharmacological effect, diabetic kidney disease, SIRT1-NF-κB pathway, renal fibrosis

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