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miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target
Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433485/ https://www.ncbi.nlm.nih.gov/pubmed/22962609 http://dx.doi.org/10.1371/journal.pone.0044305 |
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author | Aguado-Fraile, Elia Ramos, Edurne Sáenz-Morales, David Conde, Elisa Blanco-Sánchez, Ignacio Stamatakis, Konstantinos del Peso, Luis Cuppen, Edwin Brüne, Bernhard Bermejo, María Laura García |
author_facet | Aguado-Fraile, Elia Ramos, Edurne Sáenz-Morales, David Conde, Elisa Blanco-Sánchez, Ignacio Stamatakis, Konstantinos del Peso, Luis Cuppen, Edwin Brüne, Bernhard Bermejo, María Laura García |
author_sort | Aguado-Fraile, Elia |
collection | PubMed |
description | Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia. Here, we have identified several miRNAs involved in the response of the proximal tubule cell to I/R. Microarrays and RT-PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in vitro demonstrated that miR-127 is induced during ischemia and also during reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia Inducible Factor-1alpha (HIF-1α) stabilization. Moreover, miR-127 is involved in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR-127 maintains focal adhesion complex assembly and the integrity of tight junctions. miR-127 also regulates intracellular trafficking since miR-127 interference promotes dextran-FITC uptake. In fact, we have identified the Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of miR-127 in rat proximal tubule cells. In summary, we have described a novel role of miR-127 in cell adhesion and its regulation by HIF-1α. We also identified for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as key mediators of proximal epithelial tubule cell response to I/R with potential al application in renal ischemic damage management. |
format | Online Article Text |
id | pubmed-3433485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34334852012-09-07 miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target Aguado-Fraile, Elia Ramos, Edurne Sáenz-Morales, David Conde, Elisa Blanco-Sánchez, Ignacio Stamatakis, Konstantinos del Peso, Luis Cuppen, Edwin Brüne, Bernhard Bermejo, María Laura García PLoS One Research Article Ischemia/reperfusion (I/R) is at the basis of renal transplantation and acute kidney injury. Molecular mechanisms underlying proximal tubule response to I/R will allow the identification of new therapeutic targets for both clinical settings. microRNAs have emerged as crucial and tight regulators of the cellular response to insults including hypoxia. Here, we have identified several miRNAs involved in the response of the proximal tubule cell to I/R. Microarrays and RT-PCR analysis of proximal tubule cells submitted to I/R mimicking conditions in vitro demonstrated that miR-127 is induced during ischemia and also during reperfusion. miR-127 is also modulated in a rat model of renal I/R. Interference approaches demonstrated that ischemic induction of miR-127 is mediated by Hypoxia Inducible Factor-1alpha (HIF-1α) stabilization. Moreover, miR-127 is involved in cell-matrix and cell-cell adhesion maintenance, since overexpression of miR-127 maintains focal adhesion complex assembly and the integrity of tight junctions. miR-127 also regulates intracellular trafficking since miR-127 interference promotes dextran-FITC uptake. In fact, we have identified the Kinesin Family Member 3B (KIF3B), involved in cell trafficking, as a target of miR-127 in rat proximal tubule cells. In summary, we have described a novel role of miR-127 in cell adhesion and its regulation by HIF-1α. We also identified for the first time KIF3B as a miR-127 target. Both, miR-127 and KIF3B appear as key mediators of proximal epithelial tubule cell response to I/R with potential al application in renal ischemic damage management. Public Library of Science 2012-09-04 /pmc/articles/PMC3433485/ /pubmed/22962609 http://dx.doi.org/10.1371/journal.pone.0044305 Text en © 2012 Aguado-Fraile et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Aguado-Fraile, Elia Ramos, Edurne Sáenz-Morales, David Conde, Elisa Blanco-Sánchez, Ignacio Stamatakis, Konstantinos del Peso, Luis Cuppen, Edwin Brüne, Bernhard Bermejo, María Laura García miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title | miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title_full | miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title_fullStr | miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title_full_unstemmed | miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title_short | miR-127 Protects Proximal Tubule Cells against Ischemia/Reperfusion: Identification of Kinesin Family Member 3B as miR-127 Target |
title_sort | mir-127 protects proximal tubule cells against ischemia/reperfusion: identification of kinesin family member 3b as mir-127 target |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433485/ https://www.ncbi.nlm.nih.gov/pubmed/22962609 http://dx.doi.org/10.1371/journal.pone.0044305 |
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