Dioscin ameliorates peritoneal fibrosis by inhibiting epithelial-to-mesenchymal transition of human peritoneal mesothelial cells via the TLR4/MyD88/NF-κB signaling pathway

This study provides a novel and efficient remedy to alleviate PD-associated fibrosis for patients undergoing long-term peritoneal dialysis.

The human peritoneal mesothelial cell line (HMrSV5) was treated with LPS, followed by treatment with different concentrations of dioscin (0.25, 0.5 or 1.0 μg/ml). Toll-like receptor (TLR) 4 gene transfection was performed and dioscin (0.5 μg/ml) was used in mechanism research. Then morphological observation was carried out, and LPS-related markers of epithelial mesenchymal transition (EMT) as well as fibrosis markers were detected by western blotting. qRT-PCR and ELISA assay were applied to measure inflammatory factors. Furthermore, TLR4/MyD88/NF-κB pathway related proteins were assessed.

To investigate the effect of dioscin on lipopolysaccharide (LPS)-induced peritoneal fibrosis and its underlying mechanism.

Dioscin inhibited LPS-induced morphologic changes, significantly reduced the levels of markers of EMT including N-cadherin, matrix metalloproteinase-2 (MMP-2), MMP-9 and vimentin, and elevated the levels of E-cadherin and zonula occludens protein 1 (ZO-1). Decreased levels of fibrosis markers α-smooth muscle actin (α-SMA), collagen I and fibronectin were found in dioscin groups. Additionally, dioscin downregulated interleukin-6 (IL-6), IL-1β and tumor necrosis factor alpha (TNF-α). Dioscin inhibited EMT and fibrosis through triggering the TLR4/MyD88/NF-κB signaling pathway by decreasing expressions of TLR4, myeloid differentiation factor 88 (MyD88), nuclear factor κB (NF-κB), transforming growth factor-β1 (TGF-β1), phosphorylated Smad2 (p-Smad2), α-SMA, collagen I and fibronectin.