miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway
Abstract 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...
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Sociedad de Biología de Chile
2018
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oai:scielo:S0716-976020180001002272018-10-18miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathwayZhu,XiaoguangLi,WenwenLi,Huicong miR-214 Acute kidney injury Dkk3 Wnt/β-catenin signaling pathway Abstract 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.51 20182018-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100227en10.1186/s40659-018-0179-2 |
| institution |
Scielo Chile |
| collection |
Scielo Chile |
| language |
English |
| topic |
miR-214 Acute kidney injury Dkk3 Wnt/β-catenin signaling pathway |
| spellingShingle |
miR-214 Acute kidney injury Dkk3 Wnt/β-catenin signaling pathway Zhu,Xiaoguang Li,Wenwen Li,Huicong miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| description |
Abstract 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. |
| author |
Zhu,Xiaoguang Li,Wenwen Li,Huicong |
| author_facet |
Zhu,Xiaoguang Li,Wenwen Li,Huicong |
| author_sort |
Zhu,Xiaoguang |
| title |
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| title_short |
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| title_full |
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| title_fullStr |
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| title_full_unstemmed |
miR-214 ameliorates acute kidney injury via targeting DKK3 and activating of Wnt/β-catenin signaling pathway |
| title_sort |
mir-214 ameliorates acute kidney injury via targeting dkk3 and activating of wnt/β-catenin signaling pathway |
| publisher |
Sociedad de Biología de Chile |
| publishDate |
2018 |
| url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100227 |
| work_keys_str_mv |
AT zhuxiaoguang mir214amelioratesacutekidneyinjuryviatargetingdkk3andactivatingofwnt946cateninsignalingpathway AT liwenwen mir214amelioratesacutekidneyinjuryviatargetingdkk3andactivatingofwnt946cateninsignalingpathway AT lihuicong mir214amelioratesacutekidneyinjuryviatargetingdkk3andactivatingofwnt946cateninsignalingpathway |
| _version_ |
1718441574666338304 |