Paricalcitol ameliorates epithelial-to-mesenchymal transition in the peritoneal mesothelium.

Abstract

Background: The purpose of the present study was to examine the effectiveness of paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT).

Materials and methods: Human peritoneal mesothelial cells (HPMCs) were cultured in media containing transforming growth factor β1 (TGF-β1) with or without paricalcitol. Forty-two male Sprague-Dawley rats were divided into three groups. In the control group, the catheter was inserted but no dialysate was infused. The peritoneal dialysis (PD) group was infused with a conventional 4.25% dialysis solution. The paricalcitol group was infused with 4.25% dialysis solution and cotreated with paricalcitol.

Results: Exposure of HPMCs to TGF-β1 decreased the protein level of the epithelial cell marker and increased the expression levels of the mesenchymal markers. Cotreatment with paricalcitol increased the protein levels of the epithelial cell marker and decreased those of mesenchymal markers compared with their levels in cells treated with TGF-β1 alone. Exposure of HPMCs to TGF-β1 significantly increased the phosphorylation of Smad2 and Smad3. Cotreatment with paricalcitol significantly decreased the phosphorylation of Smad2 and Smad3 compared with that of cells treated with TGF-β1 alone. After 8 weeks of experimental PD in rats, the thickness of the peritoneal membrane in the PD group was significantly increased compared with that of the control group. Cotreatment with paricalcitol decreased peritoneal thickness.

Conclusion: The present study showed that paricalcitol attenuates the TGF-β1-induced EMT in peritoneal mesothelial cells. We suggest that paricalcitol may preserve peritoneal mesothelial cells during PD and could thus be of value for the success of long-term PD.