Abstract: FR-PO453
Role of Cross-Talk Between Mesothelial Cells (MCs) and Adipocytes (ACs) in Phenotype Transition of MCs in Peritoneal Dialysis (PD)
Session Information
- Peritoneal Dialysis: Current Topics
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Dialysis
- 702 Dialysis: Home Dialysis and Peritoneal Dialysis
Authors
- Kang, Hyun-Jung, Ewha Womans University, Seoul, Korea (the Republic of)
- Her, Ye rim, Ewha Womans University, Seoul, Korea (the Republic of)
- Kim, Dal-Ah, Ewha Womans University, Seoul, Korea (the Republic of)
- Kang, Duk-Hee, Ewha Womans University, Seoul, Korea (the Republic of)
Background
In peritoneal cavity, adipose tissue is buried under mesothelial monolayer and possibly interacts with neighboring MCs. Although a majority of previous work has focused on peritoneal MCs as a key player of peritoneal fibrosis, the role of neighboring ACs and their secreted adipokines in epithelial-to-mesenchymal transition (EMT) of MCs needs to be investigated.
Methods
Transwell co-culture system was used in which MCs were cultured with mature ACs differentiated from 3T3-L1 preadipocytes. EMT of MCs was evaluated by the changes in morphology and markers of epithelial and mesenchymal cells. Adipokines in supernatant and cell lysate were analyzed by adipokine array, real-time PCR, and Western blotting. Effect of stimulation or gene silencing of adipokines on EMT was examined.
Results
Co-culture of MCs and ACs induced EMT of MCs from 48 hours. Co-culture of MCs and ACs resulted in a decrease of adiponectin (0.4-fold) and plasminogen activator inhibitor-1 (PAI-1) (0.6-fold) and an increase in IL-6 (3.9-fold) and leptin (1.5-fold) in cell culture supernatant. Co-culture also led to an increased expression of monocyte chemoattractant protein-1 (MCP-1) (1.6-fold), vascular endothelial growth factor (VEGF) (2.4-fold), and PAI-1 (1.4-fold) whereas resulted in a decreased expression of adiponectin (0.9-fold) and resistin (0.8-fold) in cell lysates of ACs. Increased expression of adiponectin (83.5-fold) and PAI-1 (1.5-fold) was also observed in cell lysates of MCs. siLeptin or siPAI-1 treatment alleviated EMT of MCs whereas the treatment of IL-6 (50 ng/ml), MCP-1 (10 ng/ml), or VEGF (2 ng/ml) induced EMT of MCs.
Conclusion
ACs could induce phenotype transition of peritoneal MCs and trigger pro-fibrotic signal in peritoneal cavity. Precise mechanism for the pro-fibrotic cross-talk between MCs and ACs and the role of various adipokines which shows the different pattern of up- or down-regulation on co-culture system needs to be further investigated.