The Expression of Circ-Astn1 Inhibits High Glucose Induced Endothelial Progenitor Cell Dysfunction by Activating Autophagy.
Shiying HuangMinjie XuMaoquan LiJie ChengYongfa WuPublished in: Endocrine research (2024)
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.
Keyphrases
- high glucose
- endothelial cells
- oxidative stress
- diabetic rats
- poor prognosis
- endoplasmic reticulum stress
- signaling pathway
- cell death
- public health
- cell proliferation
- ischemia reperfusion injury
- fluorescent probe
- chronic kidney disease
- transcription factor
- flow cytometry
- aqueous solution
- binding protein
- crispr cas
- long non coding rna
- type diabetes
- skeletal muscle
- high throughput sequencing
- glycemic control
- peritoneal dialysis
- end stage renal disease
- combination therapy
- dna methylation
- copy number
- smoking cessation