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

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. Funding: Government Support – Non-U.S.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.