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eISSN: 1643-3750

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

Kang-Han Liu, Jia Fu, Nan Zhou, Wei Yin, Yi-Ya Yang, Sha-Xi Ouyang, Yu-Mei Liang

Department of Nephrology, Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China (mainland)

Med Sci Monit 2019; 25:5892-5902

DOI: 10.12659/MSM.916313

Available online: 2019-08-08

Published: 2019-08-08


#916313

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, ß-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/ß-catenin signaling pathway.

Keywords: Complement Inactivating Agents, peritoneal fibrosis, Wnt Signaling Pathway



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