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miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/ß-catenin signaling pathway.
Biol Res ; 51(1): 31, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-30180910
ABSTRACT

BACKGROUND:

miR-214 was demonstrated to be upregulated in models of renal disease and promoted fibrosis in renal injury independent of TGF-ß 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 (IL)-1ß, IL-6, were detected by RT-qPCR. The protein levels of Bcl-2, Bax, Dickkopf-related protein 3, ß-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/ß-catenin signaling. Moreover, miR-214 ameliorated AKI in vivo by inhibiting apoptosis and fibrosis through targeting Dkk3 and activating Wnt/ß-catenin pathway.

CONCLUSION:

miR-214 ameliorates AKI by inhibiting apoptosis through targeting Dkk3 and activating Wnt/ß-catenin signaling pathway, offering the possibility of miR-214 in the therapy of ischemic AKI.
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Texto completo: Disponível Coleções: Bases de dados internacionais Base de dados: MEDLINE Assunto principal: Peptídeos e Proteínas de Sinalização Intercelular / MicroRNAs / Cateninas / Lesão Renal Aguda / Via de Sinalização Wnt Limite: Animais Idioma: Inglês Revista: Biol Res Assunto da revista: Biologia Ano de publicação: 2018 Tipo de documento: Artigo País de afiliação: China