1. Effect of Tang-Shen-Ning decoction on podocyte epithelial-esenchymal transformation via inhibiting Wnt/β-catenin pathway in diabetic mice
- Author
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Zhen Cai, Yanbin Gao, Wen-Jing Zhao, Yue-Fen Wang, Cun Shen, Xin-Can Jiang, Yuan Meng, and Fang-Qiang Cui
- Subjects
0301 basic medicine ,Epithelial-Mesenchymal Transition ,Diabetes Mellitus, Experimental ,Podocyte ,Diabetic nephropathy ,Nephrin ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Western blot ,Animals ,Medicine ,Diabetic Nephropathies ,Wnt Signaling Pathway ,Advanced and Specialized Nursing ,biology ,medicine.diagnostic_test ,Podocytes ,business.industry ,Wnt signaling pathway ,medicine.disease ,Molecular biology ,Rats ,030104 developmental biology ,Anesthesiology and Pain Medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Catenin ,biology.protein ,Synaptopodin ,Desmin ,business ,Drugs, Chinese Herbal - Abstract
Background Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). Podocyte epithelial-esenchymal transformation (EMT) induced by the activated Wnt/β-catenin pathway plays a key role in DN. Tang-Shen-Ning (TSN), a Chinese herbal formula, has been shown to decrease proteinuria and protect the renal function in DN. However, the effect of TSN on the Wnt/β-catenin pathway and podocyte EMT is unclear. Methods TSN was orally administrated in KK-Ay mice for 4 weeks, at a daily dose of 20 g/kg body weight in our in vivo study. Rat serum containing TSN was added in podocyte cultured in high glucose for 24 h. The levels of 24 h urine protein, serum creatinine and blood urea nitrogen were detected by ELISA. Nephrin, Synaptopodin, P-cadherin, desmin, FSP-1, and collagen I protein and mRNA expressions were detected by western blot, immunohistochemistry, immunofluorescence, and RT-PCR. Snail, β-catenin, and TCF/LEF were detected by Western blot, RT-PCR and luciferase. Results TSN significantly decreased 24-h urine protein, serum creatinine, and blood urea nitrogen in DN mice. Further, TSN also significantly increased the expression of nephrin, synaptopodin, and P-cadherin, while the expression of desmin, fibroblast-specific protein 1 (FSP-1), and collagen I of podocytes was significantly decreased. Moreover, TSN significantly inhibited the activation of the Wnt/β-catenin pathway in podocytes cultured under high glucose (HG). Notably, the effect of TSN on podocyte EMT was reversed by activation of the Wnt/β-catenin pathway. Conclusions TSN could protect podocytes from injury in DN, partly via inhibiting the activation of the Wnt/β-catenin pathway and ameliorating podocyte EMT.
- Published
- 2021