Sanziguben Polysaccharides Attenuate Renal Epithelial-Mesenchymal Transition in Diabetic Nephropathy through Nrf2-Mediated Regulation of TGF-β1/Smad7 Signaling Pathway

Abstract

Context. Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. Objectives. Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. Materials and Methods. In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF-β1-induced EMT in HK-2 cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2 cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. Results. In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF-β1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2 cell epithelial-mesenchymal transition induced by HG combined with TGF-β1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF-β1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2 cells were weakened. Conclusions. The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF-β1/Smad7 signaling pathway.