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Published on: June 12, 2017
The Expression of Circ-Astn1 Inhibits High Glucose Induced Endothelial Progenitor Cell Dysfunction by Activating
Shiying Huang1,2, Minjie Xu1,3, Maoquan Li1,3
1Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, Shanghai, China.
Background:
Diabetes mellitus (DM) and complications such as chronic kidney disease and cardiovascular symptoms pose a substantial public health burden. Increasing studies have shown that circular RNAs (circRNAs) regulate many gene expressions that are essential in diverse pathological and biological procedures. However, the roles of particular circRNAs in DM are unclear.
Methods:
In the current investigation, endothelial progenitor cells (EPCs) were used to search for abnormal expression of circRNAs by using high-throughput sequencing under high glucose (HG) conditions. The regulatory mechanisms and targets were then studied through bioinformatics analysis, luciferase reporter analysis, angiogenic differentiation experiments, flow cytometry detection of apoptosis and RT-qPCR analysis.
Results:
The circ-Astn1 expression in EPCs decreased after HG treatment. Overexpression or circ-Astn1 suppressed HG induced endothelial cell damage. MicroRNA (miR)-138-5p and SIRT5 were found to be the downstream targets of circ-Astn1 through luciferase reporter analysis. SIRT5 downregulation or miR-138-5p overexpression reversed circ-Astn1's protective effect against HG induced endothelial cell dysfunction, including apoptosis and abnormal vascular differentiation. Furthermore, circ-Astn1 overexpression promoted autophagy activation by increasing SIRT5 expression under HG conditions. Our findings suggest that circ-Astn1 mediated promotion of SIRT5 facilitates autophagy by sponging miR-138-5p.
Conlusion:
Together, our findings show that the overexpression of circ-Astn1 suppresses HG induced endothelial cell damage by targeting miR-138-5p/SIRT5 axis.
Insights
Circular RNA circ-Astn1 protects against high glucose-induced endothelial cell damage in diabetes. It targets the miR-138-5p/SIRT5 pathway, promoting autophagy and suppressing apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Diabetes mellitus (DM) and its complications represent a significant global health challenge.
- Circular RNAs (circRNAs) are emerging as key regulators of gene expression in various biological processes.
- The specific roles of circRNAs in the pathogenesis of DM remain largely unexplored.
Purpose of the Study:
- To investigate the expression and function of circRNAs in endothelial progenitor cells (EPCs) under high glucose (HG) conditions relevant to DM.
- To elucidate the molecular mechanisms underlying the role of circ-Astn1 in HG-induced endothelial cell dysfunction.
Main Methods:
- High-throughput sequencing of circRNAs in EPCs exposed to HG.
- Bioinformatics analysis to identify potential targets and regulatory pathways.
- Luciferase reporter assays, angiogenic differentiation assays, flow cytometry for apoptosis, and RT-qPCR to validate findings.
Main Results:
- circ-Astn1 expression was downregulated in EPCs under HG conditions.
- Overexpression of circ-Astn1 protected endothelial cells from HG-induced damage, including apoptosis and impaired vascular differentiation.
- circ-Astn1 was found to target both miR-138-5p and SIRT5, with SIRT5 upregulation and autophagy promotion observed.
Conclusions:
- circ-Astn1 plays a protective role against high glucose-induced endothelial cell damage in diabetes.
- The protective mechanism involves targeting the miR-138-5p/SIRT5 axis, enhancing SIRT5 expression, and promoting autophagy.
- circ-Astn1 represents a potential therapeutic target for managing diabetic vascular complications.
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