Abstract: SA-PO929
Attenuation of Glucose-Induced Inflammatory Reaction by Blocking of TonEBP in Primary Cultured Human Peritoneal Mesothelial Cells
Session Information
- Dialysis: Peritoneal Dialysis - III
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 703 Dialysis: Peritoneal Dialysis
Authors
- Jeon, Un Sil, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah, United Arab Emirates
- Kim, Yon Su, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
- Yang, Seung Hee, Kidney Research Institute, Seoul National University, Seoul, Korea (the Republic of)
Background
Long-term exposure to high-glucose concentration in peritoneal dialysate can cause peritoneal damage by inflammatory reaction and fibrosis in the peritoneum, which finally leads to withdrawal from peritoneal dialysis.
Recently, it is known that tonicity induced transcriptional activator, TonE binding protein (TonEBP), is involved in the pathogenesis of diabetic complications such as retinopathy and nephropathy (Cardiovasc Diabetol. 2016 Jan 29;15:18, J Am Soc Nephrol. 2018 Feb;29(2):492-504).
Methods
Here, we examined the role of TonEBP in glucose induced inflammation using primary cultured human peritoneal mesothelial cells (HPMCs). HPMCs were isolated from peritoneal effluents of patients on peritoneal dialysis. Isolation and characterization of HPMCs were verified by cobblestone like characteristic morphology and the expression of the standard mesothelial markers.
Results
First, we observed that both high concentration of NaCl and 2% glucose induced increase in TonEBP mRNA expression and activation of TonEBP by nuclear translocation in cultured HPMCs. Aldose reductase (AR) mRNA expression, a target gene of TonEBP, was increased by high NaCl and glucose as expected. The treatment of NaCl and glucose increased in abundance of p65, NF-κB protein, but did not induce nuclear translocation of it. The gene expression of inflammatory markers such as IL-6, IL-8, MCP-1 and IκB was increased in culture HPMCs by high glucose treatment. High glucose also increased cytokine levels of IL-6, IL-8 and MCP-1 in supernatant of HPMCs.
Next, we examined the role of TonEBP in those inflammatory reactions by blocking of TonEBP using TonEBP disrupted MEF cells and TonEBP siRNA in HPMCs. IL-6 and IL-8 mRNA expression was decreased in both TonEBP disrupted MEF cells and TonEBP si-RNA treated HPMCs. However, there was discrepancy in the effect of high glucose on MCP-1 and IκB expression by TonEBP blocking between TonEBP disrupted MEF cells and TonEBP si-RNA in HPMCs.
Conclusion
Our findings suggest that TonEBP is involved in high-glucose induced inflammatory changes in the peritoneum of peritoneal dialysis patients, which could be prevented by blocking TonEBP action.