Effect of astragaloside IV and the role of nuclear receptor RXRα in human peritoneal mesothelial cells in high glucose‑based peritoneal dialysis fluids.

Abstract

Peritoneal fibrosis is a serious complication that can occur during peritoneal dialysis (PD), which is primarily caused by damage to peritoneal mesothelial cells (PMCs). The onset of peritoneal fibrosis is delayed or inhibited by promoting PMC survival and inhibiting PMC epithelial-to-mesenchymal transition (EMT). In the present study, the effect of astragaloside IV and the role of the nuclear receptor retinoid X receptor-α (RXRα) in PMCs in high glucose-based PD fluids was investigated. Human PMC HMrSV5 cells were transfected with RXRα short hairpin RNA (shRNA), or an empty vector, and then treated with PD fluids and astragaloside IV. Cell viability, apoptosis and EMT were examined using the Cell Counting Kit-8 assay and flow cytometry, and by determining the levels of caspase-3, E-cadherin and α-smooth muscle actin (α-SMA) via western blot analysis. Cell viability and apoptosis were increased, as were the levels of E-cadherin in HMrSV5 cells following treatment with PD fluid. The protein levels of α-SMA and caspase-3 were increased by treatment with PD fluid. Exposure to astragaloside IV inhibited these changes; however, astragaloside IV did not change cell viability, apoptosis, E-cadherin or α-SMA levels in HMrSV5 cells under normal conditions. Transfection of HMrSV5 cells with RXRα shRNA resulted in decreased viability and E-cadherin expression, and increased apoptosis and α-SMA levels, in HMrSV5 cells treated with PD fluids and co-treated with astragaloside IV or vehicle. These results suggested that astragaloside IV increased cell viability, and inhibited apoptosis and EMT in PMCs in PD fluids, but did not affect these properties of PMCs under normal condition. Thus, the present study suggested that RXRα is involved in maintaining viability, inhibiting apoptosis and reducing EMT of PMCs in PD fluid.