bafilomycin-a1 and Cardiovascular-Diseases

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.

Topics: Cardiovascular Diseases; Cell Line, Tumor; Cell Transformation, Neoplastic; Chromatin Immunoprecipitation; Gene Expression Regulation; Genistein; HEK293 Cells; Humans; Kruppel-Like Transcription Factors; Macrolides; Oligonucleotide Array Sequence Analysis; Promyelocytic Leukemia Zinc Finger Protein; Prorenin Receptor; Protein Kinase Inhibitors; Receptors, Cell Surface; RNA, Small Interfering; Signal Transduction; Transcriptome; Vacuolar Proton-Translocating ATPases