Drug Design, Development and Therapy (Feb 2020)
Panax Notoginseng Ameliorates Podocyte EMT by Targeting the Wnt/β-Catenin Signaling Pathway in STZ-Induced Diabetic Rats
Abstract
Ling Xie, 1, 2 Ruonan Zhai, 3 Teng Chen, 3 Chongting Gao, 3 Rui Xue, 3 Niansong Wang, 3 Jianbo Wang, 4 Youhua Xu, 5 Dingkun Gui 3 1College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, People’s Republic of China; 2Department of Nephrology, Shanghai Sixth People’s Hospital East Campus, Shanghai, People’s Republic of China; 3Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 4Department of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 5Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau, People’s Republic of ChinaCorrespondence: Dingkun GuiDepartment of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, People’s Republic of ChinaTel +86 021-64369181Email [email protected] WangDepartment of Interventional Radiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, People’s Republic of ChinaTel +86 21-6436 9181Email [email protected]: Epithelial–mesenchymal transition (EMT) may contribute to podocyte dysfunction in diabetic nephropathy (DN). Aiming to identify novel therapeutic options, we investigated the protective effects of Panax notoginseng (PN) on podocyte EMT in diabetic rats and explored its mechanisms.Methods: Diabetes was induced in rats with streptozotocin (STZ) by intraperitoneal injection at 55 mg/kg. Diabetic rats were randomly divided into three groups, namely, diabetic rats, diabetic rats treated with beraprost sodium (BPS) at 0.6 mg/kg/d or PN at 0.4 g/kg/d p.o., for 12 weeks. Urinary albumin/creatinine ratio (ACR), biochemical parameters, renal histopathology, and podocyte morphological changes were evaluated. Protein expression of EMT markers (desmin, α-SMA, and nephrin) as well as components of the Wnt/β-catenin pathway (wnt1, β-catenin, and snail) was detected by immunohistochemistry and Western blot, respectively.Results: In diabetic rats, severe hyperglycemia and albuminuria were detected. Moreover, mesangial expansion and podocyte foot process effacement were found markedly increased in diabetic kidneys. Increased protein expression of wnt1, β-catenin, snail, desmin, and α-SMA, as well as decreased protein expression of nephrin was detected in diabetic kidneys. All these abnormalities found in DN rats were partially restored by PN treatment.Conclusion: PN ameliorated albuminuria and podocyte EMT in diabetic rats partly through inhibiting Wnt/β-catenin signaling pathway. These findings provide experimental arguments for a novel therapeutic option in DN.Keywords: Panax notoginseng, diabetic nephropathy, podocyte, Wnt/β-catenin, epithelial–mesenchymal transition
