Abstract: SA-PO934
The Expression of Glucose Transporters (GLUTs) and Sodium-Glucose Co-Transporters (SGLTs) in Peritoneal Mesothelial Cell (MC) and Its Role in Phenotype Transition of MC
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
- Kang, Duk-Hee, Ewha University College of Medicine, Seoul, Korea (the Republic of)
- Ryu, Eun sun, Ewha Womans University School of Medicine, Seoul, Korea (the Republic of)
- Kim, Dal-ah, Ewha Womans University Medical Center, Seoul, SEOUL, Korea (the Republic of)
- Kang, Hyun-Jung, Ewha Womans University, Seoul, Korea (the Republic of)
Background
Phenotype transition of MCs such as epithelial-to-mesenchymal transition (EMT) by glucose or proinflammatory cytokines is known as an early mechanism of peritoneal dysfunction in peritoneal dialysis (PD). Given the consideration of high glucose concentration in peritoneal dialysate, the expressions of GLUTs and SGLTs in MC may play a role in peritoneal EMT. However, there are few data on the expression and regulation of GLUTs and SGLTs in MCs. We investigated the expression of each isoform of GLUTs and SGLTs, and their role in EMT of peritoneal MCs.
Methods
MCs were also isolated from overnight dwell dialysate effluents from clinically stable PD patients (MCs-DE) as well as omentum (MCs-OT) to assess the expression of GLUTs and SGLTs. The expressions of GLUT-1, -2 , -3, SGLT-1, and -2 were investigated by real-time PCR and Western botting. EMT was evaluated by the changes in cell morphology and expression of epithelial and mesenchymal cell markers. To investigate the role of SGLTs in peritoneal EMT, the effects of Dapagliflozin (SGLT2 inhibitor, 500nM) and Empagliflozin (SGLT 1/2 inhibitor, 500nM) were evaluated.
Results
GLUT-1, -2, -3, SGLT-1 and -2 were constitutively expressed in MC, and up-regulated by the stimulation with high glucose (HG, 60 mM) both at mRNA and protein levels. GLUT-1 and -3 were quantitatively major transporters in MCs, however HG-induced upregulation was more prominent in SGLT-1 and -2. The expression of GLUT-1, -2, SGLT-1 and -2 were higher in MCs-DE compared to MCs-OT which have never been exposed to dialysate. TGFβ also increased the expression of GLUT-1, -2, -3, SGLT-1 and -2. High glucose- and TGFβ-induced EMT in MCs-OT were ameliorated by pre-treatment with Dapagliflozin or Empagliflozin.
Conclusion
Modulation of the activity and expression of glucose transporters in MCs by specific inhibitors or glucose-sparing prescription of peritoneal dialysis could be a novel therapeutic approach to protect the peritoneum from the development of EMT and peritoneal fibrosis in PD patients.