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Abstract: SA-PO0413

Inhibition of the cGAS-STING Signaling Pathway Attenuates High Glucose-Induced Epithelial-Mesenchymal Transition in Human Peritoneal Mesothelial Cells

Session Information

Category: Dialysis

  • 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Author

  • Dong, Fuxing, Fujian Provincial Hospital, Fuzhou, Fujian, China
Background

Epithelial-mesenchymal transition (EMT) in peritoneal mesothelial cells plays a pivotal role in the development of peritoneal fibrosis. This study investigates the impact of the cGAS-STING signaling pathway on EMT in peritoneal mesothelial cells under high glucose(HG) conditions.

Methods

HMrSV5 cells exposed to high glucose were analyzed via Western blot (WB) for cGAS, STING, α-SMA, and Vimentin expression. To modulate the pathway, cells were treated with si-cGAS or the cGAS inhibitor RU.521. qPCR was performed to assess mRNA levels of cGAS-STING pathway components (cGAS, STING, IRF3, TBK1) and EMT-related genes (E-cadherin, Vimentin, α-SMA, TGF-β1). Protein expression was further confirmed by WB. Cell invasiveness was evaluated using Transwell assays, and pro-inflammatory cytokine levels (IL-6, TNF-α) in cell supernatants were quantified via ELISA.

Results

Our findings demonstrate that high glucose significantly upregulates cGAS and STING protein expression in HMrSV5 cells(Figure 1). Both si-cGAS transfection and RU.521 treatment effectively suppressed cGAS-STING pathway activation(Figure 1). Moreover, these interventions reduced cell invasiveness, lowered pro-inflammatory cytokine secretion, and downregulated EMT-related markers(Figure 2) .

Conclusion

Inhibition of the cGAS-STING pathway alleviates HG-induced EMT in HMrSV5 cells, suggesting a potential therapeutic target for peritoneal fibrosis.

Figure 1. The protein expressions of cGAS, STING, IRF3, and TBK1 in HMrSV5 cells were detected by WB.

Figure 2. cGAS silencing alleviates the expression of EMT-related proteins induced by high glucose in HMrSV5 cells.

Funding

  • Government Support – Non-U.S.

Digital Object Identifier (DOI)