Katharina Rump, Matthias Unterberg, Agnes Maria Dahlke, Hartmuth Sebastian Burkhard Nowak, Björn Koos, Lars Bergmann, Winfried Siffert, Simon Thomas Schäfer, Jürgen Peters, Michael Adamzik, Tim Rahmel
- Altered aquaporin 5 (\(\it AQP5\)) expression in immune cells impacts on key mechanisms of inflammation and is associated with sepsis survival. Since epigenetic regulation via DNA methylation might contribute to a differential \(\it AQP5\) expression in sepsis, we tested the hypotheses that DNA methylation of the \(\it AQP5\) promotor (1) influences \(\it AQP5\) expression, (2) is associated with the 30-day survival of septic patients, and (3) alters the nuclear transcription factor NF-\(\kappa\)B binding. \(\it AQP5\) mRNA expression was quantified by real-time PCR in whole blood samples of 135 septic patients. \(\textit {In silico}\) computer analysis of the \(\it AQP5\) promoter (nt-567 to nt-975) revealed seven putative inflammatory transcription factor binding sites and methylation of these sites was analyzed. Electrophoretic mobility shift assays were performed to assess the binding of nuclear NF-\(\kappa\)B to the \(\it AQP5\) promoter region nt-937. After adjustment for multiple testing, a greater methylation rate was found at cytosine site nt-937 in the \(\it AQP5\) promoter linked to NF-\(\kappa\)B binding in non-survivors compared to survivors (p = 0.002, p\(_{adj}\) = 0.014). This was associated with greater \(\it AQP5\) mRNA expression in non-survivors (p = 0.037). Greater (\(\geq\)16%) promoter methylation at nt-937 was also associated with an independently increased risk of death within 30 days (HR: 3.31; 95% CI: 1.54–6.23; p = 0.002). We detected a functionally important \(\it AQP5\) promoter cytosine site (nt-937) linked to the binding of the inflammatorily acting nuclear transcription factor NF-\(\kappa\)B, with increased methylation in sepsis non-survivors. Thus, nt-937 \(\it AQP5\) promoter methylation, presumably related to NF-\(\kappa\)B binding, is prognostically relevant in sepsis and demonstrates that epigenetic changes impact on sepsis outcome.
MetadatenAuthor: | Katharina RumpORCiDGND, Matthias UnterbergORCiDGND, Agnes Maria DahlkeGND, Hartmuth Sebastian Burkhard NowakORCiDGND, Björn KoosORCiDGND, Lars BergmannORCiDGND, Winfried SiffertGND, Simon Thomas SchäferGND, Jürgen PetersGND, Michael AdamzikORCiDGND, Tim RahmelORCiDGND |
---|
URN: | urn:nbn:de:hbz:294-77475 |
---|
DOI: | https://doi.org/10.1038/s41598-019-55051-8 |
---|
Parent Title (English): | Scientific reports |
---|
Publisher: | Springer Nature |
---|
Place of publication: | Berlin |
---|
Document Type: | Article |
---|
Language: | English |
---|
Date of Publication (online): | 2021/01/08 |
---|
Date of first Publication: | 2019/12/06 |
---|
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
---|
Tag: | Open Access Fonds |
---|
Volume: | 2019 |
---|
Issue: | 9, Artikel 18511 |
---|
First Page: | 18511-1 |
---|
Last Page: | 18511-11 |
---|
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
---|
Institutes/Facilities: | Knappschaftskrankenhaus Bochum, Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie |
---|
Dewey Decimal Classification: | Technik, Medizin, angewandte Wissenschaften / Medizin, Gesundheit |
---|
open_access (DINI-Set): | open_access |
---|
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |
---|