Polydatin impairs mitochondria fitness and ameliorates podocyte injury by suppressing Drp1 expression

• Published in: Journal of cellular physiology 2017-10, Vol.232 (10), p.2776-2787
• Main Authors: Ni, Zheng, Tao, Liang, Xiaohui, Xu, Zelin, Zhao, Jiangang, Liu, Zhao, Song, Weikang, Huo, Hongchao, Xu, Qiujing, Wang, Xin, Li
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - drug effects; Blood Glucose - metabolism; Cell Line; Cytoprotection; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic nephropathy; Disease Models, Animal; Down-Regulation; Dynamin; Dynamins - genetics; Dynamins - metabolism; dynamin‐related protein 1; Fitness; Glucosides - pharmacology; Hyperglycemia; Mice, Inbred C57BL; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial Dynamics - drug effects; Nephropathy; Original; Original s; Podocytes - drug effects; Podocytes - metabolism; Podocytes - pathology; polydatin; Reactive oxygen species; Reactive Oxygen Species - metabolism; Renal function; Resveratrol; Retarding; RNA Interference; Rodents; Signal Transduction - drug effects; Stilbenes - pharmacology; Transfection
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.25943

Polydatin (PD), a resveratrol glycoside, has been shown to protect renal function in diabetic nephropathy (DN), but the underlying molecular mechanism remains unclear. This study demonstrates that PD stabilize the mitochondrial morphology and attenuate mitochondrial malfunction in both KKAy mice and in hyperglycemia (HG)‐induced MPC5 cells. We use Western blot analysis to demonstrate that PD reversed podocyte apoptosis induced by HG via suppressing dynamin‐related protein 1 (Drp1). This effect may depend on the ability of PD to inhibit the generation of cellular reactive oxygen species (ROS). In conclusion, we demonstrate that PD may be therapeutically useful in DN, and that, podocyte apoptosis induced by HG can be reversed by PD through suppressing Drp1 expression. Our findings provide new insights into the pathogenic process of HG‐induced podocyte injury and also identify a new therapeutic target of ROS/Drp1/mitochondrial fission/apoptosis pathway for diabetic nephropathy.