title: Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
abstract: 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.
authors.affiliation: Center for Cardiovascular Research, CCR/Institute of Pharmacology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Zaade
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schmitz
authors.forename: Eileen
authors.initials: E
authors.lastname: Benke
authors.forename: Sabrina
authors.initials: S
authors.lastname: Klare
authors.forename: Kerstin
authors.initials: K
authors.lastname: Seidel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kirsch
authors.forename: Petra
authors.initials: P
authors.lastname: Goldin-Lang
authors.forename: Frank S
authors.initials: FS
authors.lastname: Zollmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
authors.forename: Heiko
authors.initials: H
authors.lastname: Funke-Kaiser
mesh_terms: D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D018942:Macrolides / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D051741:Kruppel-Like Transcription Factors; D018942:Macrolides; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; C092037:ZBTB16 protein, human; C040929:bafilomycin A1; D019833:Genistein; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor