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]₂D3) in preventing fibrosis, but the potential mechanisms remain unknown. This study aimed to investigate the role of 1,25(OH)₂D3 in epithelial-mesenchymal transition (EMT) and the downstream signaling pathway in HMrSV5 human peritoneal mesothelial cells in vitro.

MATERIAL AND 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)₂D3, 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, β-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)₂D3 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)₂D3.

CONCLUSIONS: In HMrSV5 human peritoneal mesothelial cells, 1,25(OH)₂D3 reversed EMT by inhibiting the expression of HDAC3 and upregulating VDR gene expression via the Wnt/β-catenin signaling pathway.

Keywords: Complement Inactivating Agents, peritoneal fibrosis, Calcitriol, Epithelium, Fibrosis, Histone Deacetylases, Peritoneum, Receptors, Calcitriol