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Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)R...

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Autores principales: Zaade, Daniela, Schmitz, Jennifer, Benke, Eileen, Klare, Sabrina, Seidel, Kerstin, Kirsch, Sebastian, Goldin-Lang, Petra, Zollmann, Frank S., Unger, Thomas, Funke-Kaiser, Heiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587649/
https://www.ncbi.nlm.nih.gov/pubmed/23469216
http://dx.doi.org/10.1371/journal.pone.0057674
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author Zaade, Daniela
Schmitz, Jennifer
Benke, Eileen
Klare, Sabrina
Seidel, Kerstin
Kirsch, Sebastian
Goldin-Lang, Petra
Zollmann, Frank S.
Unger, Thomas
Funke-Kaiser, Heiko
author_facet Zaade, Daniela
Schmitz, Jennifer
Benke, Eileen
Klare, Sabrina
Seidel, Kerstin
Kirsch, Sebastian
Goldin-Lang, Petra
Zollmann, Frank S.
Unger, Thomas
Funke-Kaiser, Heiko
author_sort Zaade, Daniela
collection PubMed
description The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis.
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spelling pubmed-35876492013-03-06 Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses Zaade, Daniela Schmitz, Jennifer Benke, Eileen Klare, Sabrina Seidel, Kerstin Kirsch, Sebastian Goldin-Lang, Petra Zollmann, Frank S. Unger, Thomas Funke-Kaiser, Heiko PLoS One Research Article The (pro)renin receptor ((P)RR) signaling is involved in different pathophysiologies ranging from cardiorenal end-organ damage via diabetic retinopathy to tumorigenesis. We have previously shown that the transcription factor promyelocytic leukemia zinc finger (PLZF) is an adaptor protein of the (P)RR. Furthermore, recent publications suggest that major functions of the (P)RR are mediated ligand-independently by its transmembrane and intracellular part, which acts as an accessory protein of V-ATPases. The transcriptome and recruitmentome downstream of the V-ATPase function and PLZF in the context of the (P)RR are currently unknown. Therefore, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (P)RR, stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR. We were able to identify distinct and overlapping genetic signatures as well as novel real-time PCR-validated target genes of the different molecular functions of the (P)RR. Moreover, bioinformatic analyses of our data confirm the role of (P)RŔs signal transduction pathways in cardiovascular disease and tumorigenesis. Public Library of Science 2013-03-04 /pmc/articles/PMC3587649/ /pubmed/23469216 http://dx.doi.org/10.1371/journal.pone.0057674 Text en © 2013 Zaade 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
Zaade, Daniela
Schmitz, Jennifer
Benke, Eileen
Klare, Sabrina
Seidel, Kerstin
Kirsch, Sebastian
Goldin-Lang, Petra
Zollmann, Frank S.
Unger, Thomas
Funke-Kaiser, Heiko
Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title_full Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title_fullStr Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title_full_unstemmed Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title_short Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses
title_sort distinct signal transduction pathways downstream of the (p)rr revealed by microarray and chip-chip analyses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3587649/
https://www.ncbi.nlm.nih.gov/pubmed/23469216
http://dx.doi.org/10.1371/journal.pone.0057674
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