circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy.

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.