circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy
circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy
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circ_0037128/miR-17-3p/AKT3轴促进糖尿病肾病的发展。
DOI：
10.1016/j.gene.2020.145076
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发表时间：
2021-01-10
期刊：
影响因子：
3.5
通讯作者：
Huang, Shan
中科院分区：
文献类型：
--
作者：
Wang, Qianqian;Cang, Zheng;Huang, Shan
环状RNA（circRNA）在糖尿病肾病（DN）的发生发展中起着重要作用。在这项研究中，我们研究了circ_0037128的功能及其调节糖尿病肾病发展的分子机制。结果发现，在小鼠DN模型和高糖处理的系膜细胞（MC）中，circ_0037128的表达显著增加，并且circ_0037128功能丧失导致细胞增殖减少和纤维化。此外，miR-17- 3 p作为竞争性内源RNA（ceRNA），通过其miRNA应答元件（MRE）与circ_0037128直接相互作用。结论：在DN模型中，miR-17- 3 p的表达显著下调，对细胞增殖和纤维化有负调节作用。进一步的研究发现AKT 3是miR-17- 3 p的假定靶点，其在DN模型中表达升高。总之，我们已经表征了新的circ_0037128的功能，并阐明了circ_0037128-miR-17- 3 p-AKT 3轴在DN发病机制中的意义。
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.