Silencing circ_0080425 alleviates high-glucose-induced endothelial cell dysfunction in diabetic nephropathy by
Linping Zhang1, Gang Jin1, Wei Zhang1
1Kidney Disease and Dialysis Center, Shaanxi Provincial People's Hospital, No. 256 Youyi West Road, Beilin District, Xi'an, 710068, Shaanxi, China.
Insights
Circular RNA hsa_circ_0080425 exacerbates high-glucose-induced endothelial cell injury in diabetic nephropathy. Targeting the circ_0080425/miR-140-3p/FN1 pathway offers a potential therapeutic strategy for diabetic nephropathy.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Diabetic nephropathy (DN) is a serious complication of diabetes.
- The role of hsa_circ_0080425 (circ_0080425) in DN progression is unclear.
Purpose of the Study:
- To investigate the mechanism of circ_0080425 in high-glucose-induced endothelial cell injury.
- To explore the potential of the circ_0080425/miR-140-3p/FN1 axis as a therapeutic target for DN.
Main Methods:
- Human umbilical vein endothelial cells (HRGEC) were treated with high glucose (HG).
- Cell proliferation, apoptosis, cell cycle, and wound healing were assessed.
- Expression levels of circ_0080425, miR-140-3p, and fibronectin 1 (FN1) were quantified.
- Molecular interactions were confirmed using dual-luciferase reporter assays.
Main Results:
- HG induced endothelial cell dysfunction, including inhibited proliferation and wound healing, and increased apoptosis.
- Circ_0080425 expression was upregulated by HG and contributed to cell injury.
- Circ_0080425 sponged miR-140-3p, which in turn targeted FN1.
- Knockdown of circ_0080425 or overexpression of miR-140-3p/inhibition of FN1 attenuated HG-induced injury.
Conclusions:
- Circ_0080425 promotes HG-induced endothelial cell injury.
- The circ_0080425/miR-140-3p/FN1 axis is a key pathway in DN pathogenesis.
- This axis represents a potential therapeutic target for DN.
Background:
Hsa_circ_0080425 (circ_0080425) is newly identified to correlate with the progression of diabetic nephropathy (DN). However, its role and mechanism in DN process is not very clear.
Methods:
Cell counting kit-8 assay, flow cytometry, scratch wound assay, and western blotting were performed to measure endothelial cell dysfunction. Expression of circ_0080425, microRNA (miR)-140-3p and fibronectin 1 (FN1) were determined by quantitative real-time PCR and western blotting. The direct interaction was confirmed by dual-luciferase reporter assay.
Results:
High-glucose (HG) treatment could induce inhibition of cell proliferation, cell cycle entrance and wound healing rate in human umbilical vein endothelial cells (HRGEC), and enhancement of apoptosis rate. Circ_0080425 expression was upregulated by HG, and exhausting circ_0080425 could attenuate HG-induced above effects in HRGEC. MiR-140-3p was sponged by circ_0080425, and its inhibitor reversed the regulation of circ_0080425 knockdown on HG-induced HRGEC injury. FN1 was targeted by miR-140-3p, and its overexpression also restored the inhibitory effect of miR-140-3p on HC-induced HRGEC injury.
Conclusion:
Circ_0080425 expression might contribute to HG-induced endothelial cell injury, and circ_0080425/miR-140-3p/FN1 axis was a potential therapeutic approach to interfere DN process.
