title: The Transcription Factor NMP4 Binds to the AQP5 Promoter and Is a Novel Transcriptional Regulator of the AQP5 Gene.
abstract: Aquaporin 5 (AQP5) is a water channel that regulates water transport, cell migration, and proliferation. Therefore, knowledge of its genetic regulation could be relevant to study these mechanisms. The AQP5 promoter region containing the AQP5-1364 A/C single-nucleotide polymorphism (SNP) might be an important regulatory region because the SNP is associated with the etiopathology of several diseases. The aim of this study was to identify a transcription factor that binds to this AQP5 promoter region and to investigate its potential impact upon AQP5 expression. In silico analysis revealed nuclear matrix protein 4 (NMP4) as a putative candidate. Electrophoretic mobility shift assays showed specific binding of NMP4 to the AQP5 promoter region of nt -1370 to nt -1329. Overexpression of NMP4 increased AQP5 promoter activity of the analyzed promoter constructs from nt -469 to nt -1979. Furthermore, an additional NMP4 binding site at position nt -592/nt -602 of the AQP5 promoter was identified. NMP4 overexpression increased AQP5 mRNA expression by 2.5-fold in HEK293 cells. Summarizing, we identified NMP4 as a novel transcriptional regulator of AQP5 expression, which binds to two AQP5 promoter regions. Both regions appear to impact AQP5 expression significantly.
authors.affiliation: 1 Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer der Ruhr-Universität Bochum , Bochum, Germany .|2 Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen , Essen, Germany .|3 Institut für Pharmakogenetik, Universität Duisburg-Essen, Universitätsklinikum Essen , Essen, Germany .
authors.forename: Katharina
authors.initials: K
authors.lastname: Rump
authors.affiliation: 3 Institut für Pharmakogenetik, Universität Duisburg-Essen, Universitätsklinikum Essen , Essen, Germany .
authors.forename: Winfried
authors.initials: W
authors.lastname: Siffert
authors.affiliation: 2 Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen , Essen, Germany .
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
authors.affiliation: 1 Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum Knappschaftskrankenhaus Bochum-Langendreer der Ruhr-Universität Bochum , Bochum, Germany .|2 Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen , Essen, Germany .
authors.forename: Michael
authors.initials: M
authors.lastname: Adamzik
mesh_terms: D051402:Aquaporin 5 / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051402:Aquaporin 5; D012333:RNA, Messenger; D015534:Trans-Activators; C498621:ZNF384 protein, human