miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/ß-catenin signaling pathway
Biol. Res
;
51: 31, 2018. graf
Artículo
en Inglés
| LILACS
| ID: biblio-983936
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.
Texto completo:
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Índice:
LILACS (Américas)
Asunto principal:
Péptidos y Proteínas de Señalización Intercelular
/
MicroARNs
/
Cateninas
/
Lesión Renal Aguda
/
Vía de Señalización Wnt
Tipo de estudio:
Estudio pronóstico
Límite:
Animales
Idioma:
Inglés
Revista:
Biol. Res
Asunto de la revista:
Biologia
Año:
2018
Tipo del documento:
Artículo
País de afiliación:
China
Institución/País de afiliación:
Huaihe Hospital of Henan University/CN
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