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Biological Research

Print version ISSN 0716-9760

Abstract

ZHU, Xiaoguang; LI, Wenwen  and  LI, Huicong. miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway. Biol. Res. [online]. 2018, vol.51, 31.  Epub Oct 15, 2018. ISSN 0716-9760.  http://dx.doi.org/10.1186/s40659-018-0179-2.

Background:

miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-β signaling in vivo. However, the detailed role of miR-214 in acute kidney injury (AKI) and its underlying mechanism are still largely unknown.

Methods:

In this study, an I/R-induced rat AKI model and a hypoxia-induced NRK-52E cell model were used to study AKI. The concentrations of kidney injury markers serum creatinine, blood urea nitrogen, and kidney injury molecule-1 were measured. The expressions of miR-214, tumor necrosis factor-α, interleukin (Ε)-1β, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, β-catenin, c-myc, and cyclinD1 were determined by western blot. Cell apoptosis and caspase 3 activity were evaluated by flow cytometry analysis and caspase 3 activity assay, respectively. Luciferase reporter assay was used to confirm the interaction between miR-214 and Dkk3.

Results:

miR-214 expression was induced in ischemia-reperfusion (I/R)-induced AKI rat and hypoxic incubation of NRK-52E cells. Overexpression of miR-214 alleviated hypoxia-induced NRK-52E cell apoptosis while inhibition of miR-214 expression exerted the opposite effect. Dkk3 was identified as a target of miR-214. Anti-miR-214 abolished the inhibitory effects of DKK3 knockdown on hypoxia-induced NRK-52E cell apoptosis by inactivation of Wnt/β-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/β -catenin pathway.

Conclusion:

miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/β -catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI.

Keywords : miR-214; Acute kidney injury; Dkk3; Wnt/β-catenin signaling pathway.

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