1,25-Dihydroxyvitamin D3 Prevents Epithelial-Mesenchymal Transition of HMrSV5 Human Peritoneal Mesothelial Cells by Inhibiting Histone Deacetylase 3 (HDAC3) and Increasing Vitamin D Receptor (VDR) Expression Through the Wnt/β-Catenin Signaling Pathway

Background: Peritoneal dialysis is the most common treatment for end-stage renal disease. However, peritoneal fibrosis resulting from long-term peritoneal dialysis restricts peritoneal ultrafiltration. Previous studies have shown a role for 1,25-dihydroxyvitamin D3 (1,25[OH](2)D3) in preventing fibrosis, but the potential mechanisms remain unknown. This study aimed to investigate the role of 1,25(OH)(2)D3 in epithelial-mesenchymal transition (EMT) and the downstream signaling pathway in HMrSV5 human peritoneal mesothelial cells in vitro. Material/Methods: An in vitro cell model of peritoneal fibrosis was established using the HMrSV5 human peritoneal mesothelial cell line. High glucose and lipopolysaccharide (LPS) culture conditions, with or without 1,25(OH)(2)D3, were used. Wnt agonist 1, a Wnt signaling pathway activator, was applied. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to measure the vitamin D receptor (VDR) and histone deacetylase 3 (HDAC3) gene and protein expression levels, beta-catenin, and EMT-associated biomarkers. Results: High glucose plus LPS culture medium inhibited cell proliferation, induced cell apoptosis and promoted EMT in HMrSV5 cells, which was reversed by 1,25(OH)(2)D3 by down-regulation of HDAC3 and upregulation of VDR. HDAC3 inhibited VDR gene expression. The expression of EMT-associated biomarkers was increased by Wnt agonist 1 and inhibited by 1,25(OH)(2)D3. Conclusions: In HMrSV5 human peritoneal mesothelial cells, 1,25(OH)(2)D3 reversed EMT by inhibiting the expression of HDAC3 and upregulating VDR gene expression via the Wnt/beta-catenin signaling pathway.