Abstract: FR-PO0170
Endothelial AGO1 Inhibition Delays the Progression of Diabetic Kidney Disease Through Regulation of Post-Transcriptional Gene Silencing
Session Information
- Diabetic Kidney Disease: Metabolic, Mitochondrial, and Inflammatory Mechanisms
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Author
- Fan, Qiuling, Shanghai General Hospital, Shanghai, China
Background
Diabetic kidney disease (DKD) is one of the leading causes of end-stage kidney disease worldwide. Glomerular endothelial dysfunction, chronic inflammation, and extracellular matrix (ECM) accumulation are key pathological features contributing to DKD progression. Argonaute 1 (AGO1), a core component of the RNA-induced silencing complex (RISC), plays a critical role in post-transcriptional gene regulation; however, its role in DKD remains poorly understood. This study aimed to investigate the function and underlying molecular mechanisms of endothelial AGO1 in DKD progression.
Methods
In vitro, AGO1 expression was silenced in human glomerular endothelial cells (HGECs) using siRNA, followed by exposure to high-glucose (HG) conditions to establish a diabetic injury model. In vivo, endothelial cell-specific AGO1 knockout (EC-AGO1-KO) mice were generated and diabetic kidney disease was induced using a high-fat diet combined with streptozotocin (HFD+STZ). Single-cell RNA sequencing and bulk transcriptomic analysis (RNA-seq) were performed to identify AGO1-associated signaling pathways.
Results
High-glucose stimulation significantly increased AGO1 expression in HGECs. In vitro, AGO1 knockdown markedly attenuated high glucose-induced endothelial dysfunction. In vivo, EC-AGO1-KO mice exhibited significantly lower UACR, Scr, and BUN levels compared with wild-type DKD mice. Histological analysis demonstrated that endothelial AGO1 deletion substantially alleviated glomerular hypertrophy, mesangial matrix expansion, and collagen deposition. Transcriptomic and single-cell sequencing analyses further revealed that AGO1 regulates inflammatory responses and extracellular matrix remodeling pathways, suggesting a critical role for AGO1 in endothelial injury during DKD progression.
Conclusion
AGO1 is aberrantly upregulated in glomerular endothelial cells under diabetic conditions. Inhibition of AGO1 ameliorates endothelial dysfunction, suppresses inflammation and extracellular matrix accumulation, and ultimately delays glomerular injury and renal function decline in DKD. These findings identify AGO1-mediated post-transcriptional regulation as a novel mechanism in DKD pathogenesis and suggest AGO1 as a potential therapeutic target for diabetic kidney disease.