Astragaloside IV represses high glucose-induced mesangial cells activation by enhancing autophagy via SIRT1 deacetylation of NF-[kappa]B p65 subunit

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 regula...

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Published in:Drug design, development and therapy development and therapy, 2018-01, Vol.10, p.2971
Main Authors: Wang, Xiaolei, Gao, Yanbin, Tian, Nianxiu, Zhu, Zhiyao, Wang, Tao, Xu, Jiayi, Wu, Bingjie, Zhang, Nan
Format: Article
Language:English
Subjects:
Analysis
Asian medicine
Enzyme-linked immunosorbent assay
Fibrosis
Glucose
Hyperglycemia
Kidney diseases
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Summary: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-[kappa]B 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-[kappa]B pathway, indicating a potential therapeutic role of AS-IV in glomerular diseases. Keywords: Chinese medicine, pharmacological effect, diabetic kidney disease, SIRT1-NF-[kappa]B pathway, renal fibrosis
ISSN:1177-8881
1177-8881
DOI:10.2147/DDDT.S174058