Circular RNA circEIF4G2 aggravates renal fibrosis in diabetic nephropathy by sponging miR-218
Bojin Xu1, Qianqian Wang1, Wenyi Li1
1Department of Endocrinology, Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Abstract:
Circular RNAs play essential roles in the development of various human diseases. However, how circRNAs are involved in diabetic nephropathy (DN) are not fully understood. Our study aimed to investigate the effects of circRNA circEIF4G2 on DN. Experiments were performed in the db/db mouse model of type 2 diabetes and NRK-52E cells. We found that circEIF4G2 was significantly up-regulated in the kidneys of db/db mice and NRK-52E cells stimulated by high glucose. circEIF4G2 knockdown inhibited the expressions of TGF-β1, Collagen I and Fibronectin in high glucose-stimulated NRK-52E cells, which could be rescued by miR-218 inhibitor. Knockdown of SERBP1 reduced the expression of TGF-β1, Collagen I and Fibronectin in HG-stimulated NRK-52E cells. In summary, our findings suggested that circEIF4G2 promotes renal tubular epithelial cell fibrosis via the miR-218/SERBP1 pathway, presenting a novel insight for DN treatment.
Insights
Circular RNAs are implicated in diseases. This study reveals circEIF4G2 promotes diabetic nephropathy (DN) fibrosis through the miR-218/SERBP1 pathway, offering new therapeutic targets for DN.
Area of Science:
- Molecular Biology
- Genetics
- Nephrology
Background:
- Circular RNAs (circRNAs) are crucial in human disease development.
- The specific role of circRNAs in diabetic nephropathy (DN) remains unclear.
- Understanding circRNA involvement is vital for developing effective DN treatments.
Purpose of the Study:
- To investigate the role of circRNA circEIF4G2 in diabetic nephropathy (DN).
- To elucidate the molecular mechanisms underlying circEIF4G2's function in DN.
- To identify potential therapeutic targets for DN based on circRNA pathways.
Main Methods:
- Utilized a db/db mouse model for type 2 diabetes and NRK-52E kidney cells.
- Assessed circEIF4G2 expression levels in kidney tissues and high glucose-stimulated cells.
- Performed knockdown experiments for circEIF4G2 and miR-218, and SERBP1 knockdown.
Main Results:
- CircEIF4G2 expression was significantly upregulated in db/db mouse kidneys and high glucose-treated NRK-52E cells.
- Knockdown of circEIF4G2 reduced fibrosis markers (TGF-β1, Collagen I, Fibronectin) in stimulated cells.
- The effects of circEIF4G2 were mediated through the miR-218/SERBP1 pathway, as indicated by rescue experiments.
Conclusions:
- CircEIF4G2 promotes renal tubular epithelial cell fibrosis via the miR-218/SERBP1 pathway.
- This pathway represents a novel mechanism contributing to diabetic nephropathy.
- Findings suggest circEIF4G2 as a potential therapeutic target for DN treatment.
