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CircSHOC2 Knockdown Alleviates High Glucose-Induced Vascular Endothelial Cell Pyroptosis via Targeting miR-145/FOXO1
Xuying Meng1, Zhenjin Li1, Yang Li2
1Department of Endocrinology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Abstract:
Emerging evidence indicates that pyroptosis participates in the pathogenic process of vascular endothelial cells in cardiovascular system complications of diabetes. The roles of circular RNAs (circRNAs) in high glucose (HG)-induced vascular endothelial cells are still unclear. Here, our research investigated the function and mechanism of circRNA circSHOC2 in pyroptosis of vascular endothelial cells. Results indicated that circSHOC2 was up-regulated in HG-induced human umbilical vein endothelial cells (HUVECs). Functionally, cellular assays indicated that circSHOC2 silencing repressed HG-induced HUVECs pyroptosis. Moreover, circSHOC2 targeted miR-145 through miRNA sponge, and FOXO1 functioned as downstream target of miR-145. In conclusion, these findings suggested the potential roles of circSHOC2 on HG-induced vascular endothelial cells in vitro condition, providing new insights for cardiovascular system complications of diabetes.
Insights
Circular RNAs (circRNAs) like circSHOC2 are involved in high glucose-induced pyroptosis in diabetic cardiovascular complications. Silencing circSHOC2 protects vascular endothelial cells from this damage.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Diabetes Complications
Background:
- Pyroptosis contributes to vascular endothelial cell damage in diabetes.
- The role of circular RNAs (circRNAs) in high glucose (HG)-induced endothelial cell pyroptosis remains largely unknown.
- Understanding these mechanisms is crucial for addressing diabetic cardiovascular complications.
Purpose of the Study:
- To investigate the function and mechanism of circRNA circSHOC2 in pyroptosis of vascular endothelial cells.
- To explore the role of circSHOC2 in high glucose-induced endothelial cell dysfunction.
Main Methods:
- Utilized human umbilical vein endothelial cells (HUVECs) exposed to high glucose (HG).
- Assessed circSHOC2 expression levels.
- Performed functional cellular assays to evaluate the impact of circSHOC2 silencing on pyroptosis.
- Investigated the molecular interactions involving circSHOC2, miR-145, and FOXO1.
Main Results:
- circSHOC2 expression was significantly upregulated in HG-induced HUVECs.
- Silencing circSHOC2 effectively repressed HG-induced pyroptosis in HUVECs.
- Mechanistically, circSHOC2 acts as a miRNA sponge for miR-145, with FOXO1 as a downstream target of miR-145.
Conclusions:
- circSHOC2 plays a critical role in promoting pyroptosis of vascular endothelial cells under high glucose conditions.
- The circSHOC2/miR-145/FOXO1 axis is implicated in the pathogenesis of HG-induced endothelial cell injury.
- These findings offer novel insights into potential therapeutic targets for diabetic cardiovascular complications.
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