Effect of Tang-Shen-Ning decoction on podocyte epithelial-esenchymal transformation via inhibiting Wnt/β-catenin pathway in diabetic mice.

Abstract

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. 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. 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. TSN could protect podocytes from injury in DN, partly via inhibiting the activation of the Wnt/β-catenin pathway and ameliorating podocyte EMT.