Dioscin Ameliorates Peritoneal Fibrosis by Inhibiting Epithelial-to-mesenchymal Transition of Human Peritoneal Mesothelial Cells Via the TLR4/MyD88/NF-κB Signaling Pathway.

Objective: To investigate the effect of dioscin on lipopolysaccharide (LPS)-induced peritoneal fibrosis and its underlying mechanism. Methods: 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 mu g/ml). Toll-like receptor (TLR) 4 gene transfection was performed and dioscin (0.5 mu g/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-kappa B pathway related proteins were assessed. Results: 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 a-smooth muscle actin (alpha-SMA), collagen I and fibronectin were found in dioscin groups. Additionally, dioscin downregulated interleukin-6 (IL-6), IL-1 beta and tumor necrosis factor alpha (TNF-alpha). Dioscin inhibited EMT and fibrosis through triggering the TLR4/MyD88/NF-kappa B signaling pathway by decreasing expressions of TLR4, myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-kappa B), transforming growth factor-beta 1 (TGF-beta 1), phosphorylated Smad2 (p-Smad2), alpha-SMA, collagen I and fibronectin. Conclusion: This study provides a novel and efficient remedy to alleviate PD-associated fibrosis for patients undergoing long-term peritoneal dialysis.