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Kidney Week

Abstract: SA-PO681

Unveiling the Role of Mesothelial Cells in Methylglyoxal-Induced Peritoneal Fibrosis

Session Information

  • Home Dialysis - II
    November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

  • Wei, Yu-Syuan, National Taiwan University, Taipei, Taiwan
  • Tsai, Pei-Shiue Jason, National Taiwan University, Taipei, Taiwan
Background

Being one of the renal replacement therapies for end-stage kidney disease patients, peritoneal dialysis (PD) maintains the lives of about 11% of dialysis patients. However, morphological and functional changes in the peritoneum, which is called peritoneal fibrosis (PF), are inevitable during long-term PD. PF can gradually progress into ultrafiltration failure and has a high correlation with encapsulating peritoneal sclerosis, a complication with high mortality. Despite the presence of glucose degradation products (GDPs) produced by heating high glucose-containing dialysate is considered to be the key component to initiating PF, and methylglyoxal (MGO) is one of the most important GDPs; however, the mechanisms of how MGO induces PF, especially the involvement of mesothelial cells, is still unclear.

Methods

Human mesothelial cells (MeT5A), were cultured and treated with different concentrations of MGO. Cell viability and production of free radicals were evaluated first. Next-generation sequencing was then performed to assess the transcriptomic changes after MeT5A was treated with MGO for 6 hours and 24 hours. Differential expression genes (DEGs) and pathway enrichment analysis based on databases of KEGG and gene ontology (GO) were further analyzed.

Results

When compared with control MeT5A, 2009 and 2516 DEGs were detected, respectively, after 6 or 24 hours of MGO stimulation. GO enrichment analysis showed that most DEGs that appeared at 6 hours were related to extracellular matrix organization (p=0.01); while DEGs that appeared at 24 hours were related to extracellular matrix organization (p=0.00002), type I interferon signaling pathway (p=0.002), wound healing (p=0.006), cell adhesion (p=0.01) and angiogenesis (p=0.01). Although epithelial-to-mesenchymal (EMT) was considered an important phenomenon in peritoneal fibrosis, genes that related to EMT, such as SNAI1, SNAI2, CDH1, and VIM, were not significantly changed under our experimental setup. Moreover, proteins that are known to activate fibroblasts trans-differentiation into myofibroblasts, except for TGFB1, genes such as IL1B, PDGFA, PDGFB, and PDGFD were upregulated significantly.

Conclusion

Our study showed that when mesothelial cells were treated with MGO in vitro, they tended not to develop EMT but promoted pro-inflammation response and the activation of fibroblasts.

Funding

  • Government Support – Non-U.S.