TY  - JOUR
A1  - Aguado-Fraile, Elia
A1  - Ramos, Edurne
A1  - Sáenz-Morales, David
A1  - Conde, Elisa
A1  - Blanco-Sánchez, Ignacio
A1  - Stamatakis, Konstantinos
A1  - Peso, Luis del
A1  - Cuppen, Edwin
A1  - Brüne, Bernhard
A1  - García Bermejo, María Laura
T1  - miR-127 protects proximal tubule cells against ischemia/reperfusion : identification of Kinesin family member 3B as miR-127 target
T2  - PLoS One
N2  - 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.
Y1  - 2012
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/26341
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-263414
SN  - 1932-6203
VL  - 7
IS  - (9):e44305
PB  - PLoS
CY  - Lawrence, Kan.
ER  -