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circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy
Qianqian Wang1, Zheng Cang1, Lisha Shen1
1Department of Endocrinology, Shanghai Tongren Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China.
Abstract:
Circular RNAs (circRNAs) play vital roles in the development of diabetic nephropathy (DN). In this study, we investigated the function of circ_0037128 and molecular mechanism via which it regulates diabetic nephropathy development. It was found that expression of circ_0037128 was significantly increased in mouse DN model and high glucose treated mesangial cells (MCs), and circ_0037128 loss-of-function led to reduced cell proliferation and fibrosis in vitro. Moreover, miR-17-3p acts as competitive endogenous RNA (ceRNA) that directly interacts with circ_0037128 through its miRNA response elements (MREs). Consistently, expression of miR-17-3p was remarkably down-regulated in DN model, and negatively regulated cell proliferation and fibrosis. Further investigations revealed that AKT3 was the putative target of miR-17-3p, whose expression was elevated in DN model. In conclusion, we have characterized the function of a novel circ_0037128 and illustrated the significance of circ_0037128-miR-17-3p-AKT3 axis in DN pathogenesis.
Insights
Circular RNAs (circRNAs) are key in diabetic nephropathy (DN). This study reveals circ_0037128 promotes DN by regulating the miR-17-3p/AKT3 pathway, offering new therapeutic targets for DN.
Area of Science:
- Molecular Biology
- Genetics
- Nephrology
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in disease development.
- Diabetic nephropathy (DN) is a serious complication of diabetes with complex molecular underpinnings.
Purpose of the Study:
- To investigate the function of circ_0037128 in diabetic nephropathy (DN).
- To elucidate the molecular mechanism by which circ_0037128 regulates DN progression.
- To identify potential therapeutic targets for DN.
Main Methods:
- Analysis of circ_0037128 expression in a mouse DN model and high glucose-treated mesangial cells (MCs).
- Loss-of-function experiments to assess the impact of circ_0037128 on MC proliferation and fibrosis.
- Investigation of the interaction between circ_0037128 and miR-17-3p using miRNA response elements (MREs).
- Analysis of miR-17-3p and AKT3 expression in DN models.
Main Results:
- Circ_0037128 expression was significantly upregulated in DN models.
- Loss of circ_0037128 reduced MC proliferation and fibrosis.
- miR-17-3p, acting as a competing endogenous RNA (ceRNA), directly interacted with circ_0037128 and was downregulated in DN.
- AKT3, a target of miR-17-3p, was upregulated in DN.
Conclusions:
- Circ_0037128 plays a crucial role in the pathogenesis of diabetic nephropathy.
- The circ_0037128-miR-17-3p-AKT3 axis is a significant pathway in DN development.
- This axis represents a potential therapeutic target for DN treatment.
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