Ginsenoside Rg3 Reduces Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor-β1 by Inactivation of AKT in HMrSV5 Peritoneal Mesothelial Cells

Abstract

BackgroundGinsenosides, including ginsenoside Rg3, are components of Panax ginseng C.A. Meyer (Araliaceae) used in traditional Chinese medicine. Long-term peritoneal dialysis induces peritoneal fibrosis that impairs ultrafiltration and is associated with epithelial-mesenchymal transition (EMT) of peritoneal cells. This study aimed to investigate the effects of ginsenoside Rg3 on EMT induced by transforming growth factor-β1 (TGF-β1) in HMrSV5 human peritoneal mesothelial cells.Material/MethodsThe cell counting kit-8 (CCK-8) assay measured HMrSV5 cell viability. The expression of EMT markers, E-cadherin, vimentin, and α-smooth muscle actin (α-SMA) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The wound-healing assay determined cell migration. The S-phase of the cell cycle was assessed by 5-ethynyl-2′-deoxyuridine (EdU) labeling, and expression of phosphorylated AKT was measured by Western blot. The effect of ginsenoside Rg3 and the AKT activator SC79 on the TGF-β1-induced EMT of HMrSV5 cells were evaluated.ResultsLow concentration of ginsenoside Rg3 did not effect cell viability of HMrSV5 cells. TGF-β1 treatment decreased the expression of E-cadherin, and increased the expression of vimentin and α-SMA and promoted cell migration of HMrSV5 cells. However, co-treatment of ginsenoside Rg3 and TGF-β1 significantly reduced TGF-β1-induced EMT in HMrSV5 cells. TGF-β1 increased the phosphorylation of AKT and increased the expression of Smurf2. Ginsenoside Rg3 reduced TGF-β1-induced activation of AKT and Smurf2. SC79 reversed the effects of ginsenoside Rg3 on TGF-β1-induced EMT in HMrSV5 cells.ConclusionsGinsenoside Rg3 inhibited EMT induced by TGF-β1 in HMrSV5 human peritoneal mesothelial cells by inhibiting the activation of AKT.

Using the concept of food as medicine to mitigate inflammation in patients undergoing peritoneal dialysis

“…Yan et al reported that Rg3 reduced TGF‐B1 and inhibited human peritoneal cell epithelial‐mesenchymal transition (EMT) by reducing the activation of AKT and Smurf2. Thus, these results suggest that Ginsenoside Rg3 can prevent peritoneal EMT and fibrosis associated with PD [75]. In an animal model, ginsenoside Re demonstrated an anti‐inflammatory effect by inhibiting the expression of various inflammatory markers, inhibiting the expression of inflammatory markers stimulated by LPS, and inhibiting the binding of LPS to TLR4 in peritoneal macrophages [53].…”