1,25(OH)2D3 treatment attenuates high glucose‑induced peritoneal epithelial to mesenchymal transition in mice.

Abstract

It has been previously demonstrated that 1,25(OH)2D3 prevents the progression of epithelial to mesenchymal transition (EMT). However, it remains unclear whether 1,25(OH)2D3 has a role in peritoneal EMT stimulated by high glucose (HG) peritoneal dialysis fluid (PDF). The present study was performed to investigate the role of 1,25(OH)2D3 in the progression of EMT in the peritoneal mesothelium. A total of 35 male Kunming mice were randomly assigned into seven groups. In the control group, no diasylate or saline was infused. In the saline group, the mice were intraperitoneally injected with saline every day for 4 weeks. In the vitamin D group, the mice were subjected to intraperitoneal injections of 1 or 5 µg/kg of 1,25(OH)2D3 once weekly (every Monday) for 4 weeks. The peritoneal dialysis (PD) group were intraperitoneally injected with a conventional 4.25% PDF daily for 4 weeks. The vitamin D+PD group were intraperitoneally injected with 4.25% PDF daily and co-treated with 1 µg/kg or 5 µg/kg 1,25(OH)2D3 once weekly, for 4 weeks. The peritoneal morphology and thickness were assessed by hematoxylin and eosin and Masson's trichrome staining. The peritoneal protein level of EMT markers (α-smooth muscle actin, fibronectin and E-cadherin), vitamin D receptor (VDR), B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, transforming growth factor (TGF)-β and Smad3 were evaluated by western blot analysis or immunohistochemical staining. Furthermore, apoptosis was assessed using a Caspase-3 activity assay. The results demonstrated that after 4 weeks of intraperitoneal injections in mice, HG-PDF decreased the expression of VDR, promoted EMT and apoptosis, and increased the thickness of the peritoneal membrane. However, 1,25(OH)2D3 treatment attenuated HG-induced EMT and apoptosis, and decreased peritoneal thickness, which may partially occur through inhibition of transforming growth factor TGF-β/Smad pathways via 1,25(OH)2D3 binding to VDR. The present study demonstrated that 1,25(OH)2D3 attenuated HG-induced EMT and apoptosis in the peritoneal mesothelium through TGF-β/Smad pathways. 1,25(OH)2D3 treatment in conjunction with HG dialysate may provide an improved solution to the peritoneal injury in the process of PD.