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17 September 2019 : Laboratory Research

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

Xu Yan1ABC, Wei Zhang2AB, Fanwu Kong2ABC, Qianbo Li1ABCD, Wei Shan1DEFG, Chao Zhang1CD, Tingting Han1DE, Yu Che1AB, Yan Zhang1ABCDEFG*

DOI: 10.12659/MSM.915991

Med Sci Monit 2019; 25:6972-6979

Abstract

BACKGROUND: Ginsenosides, 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 AND METHODS: The 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.

RESULTS: Low 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.

CONCLUSIONS: Ginsenoside Rg3 inhibited EMT induced by TGF-β1 in HMrSV5 human peritoneal mesothelial cells by inhibiting the activation of AKT.

Keywords: Epithelial-mesenchymal transition, peritoneal fibrosis

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750